Vital Signs #6 – Oncology – May 1, 2011

By Scott Jordan, Partner — scott@c3f.ca0.myftpupload.com

 

News & Events: Cancer Stem Cells (CSCs)

 CSC’s are a subset of cells found in tumors that have the ability to self-renew and differentiate (similar to embryonic and adult stem cells in healthy tissue) leading to tumor initiation and growth, recurrence and metastasis.  However, in contrast to normal stem cells, CSC’s have oncogenic mutations resulting in the loss of normal limitations on growth. These mutations enable CSC’s to be resistant to both standard chemotherapy and radiotherapy and have an ability to migrate from the original tumor site increasing the probability of tumor recurrence. Current treatments may initially decrease the size of a tumor but they often leave behind an increased proportion of the most malignant cells.

Maintenance and migration of cancer stem cells is supported by EMT or Epithelial-Mesenchymal Transition. EMT is a program development of biological cells characterized by loss of cell adhesion, repression of E-cadherin expression, and increased cell mobility (characteristic feature of cells undergoing proliferation). The presence of EMT markers at the tumor-host interface provides strong evidence that EMT occurs during tumor development and that it regulates invasiveness and tumor aggressiveness.

Of interest is the ability of stromal cells (oftentimes comprising up to 50-70% of tumor masses) to induce EMT in tumor cells by stimulating mesenchmal cell growth and survival. Tumor cells having acquired a more mesenchymal like phenotype, have shown increased invasion and metastasis, resistance to chemotherapy and radiation induced DNA damage, increased interaction with stromal inflammatory mechanisms, and increased cell survival.

 

Company Profile: Immunocellular Cellular Therapeutics Ltd. (OTC: IMUC.OB) 

ImmunoCellular, a Los Angeles based biotechnology company, is attempting to harness the native immune system to attack CSCs without harming healthy tissue. ImmunoCellular’s lead compound, ICT-107 is in a double blinded, placebo controlled, 2:1 randomized Phase 2 designed to evaluate the safety and efficacy of ICT-107 in patients newly diagnosed with GBM (brain cancer). The study will enroll approximately 100 patients and will be conducted at an estimated 15 clinical trial centers in the U.S. in collaboration with leading experts and opinion leaders in neuro-oncology.

ICT-107 is an autologous, or personalized, dendritic cell-based vaccine that works by activating a patient’s immune system against specific tumor-associated antigens. This is accomplished by extracting dendritic cells from a patient, loading them with the antigens, and reintroducing them to the patient’s body to trigger an immune response.

ICT-107’s Value Proposition:

  1. Compelling Phase I/II Study Results

ICT-107 increased overall survival and decreased cancer recurrence in a Phase1/2 study (Data presented at American Academy of Neurology Annual Meeting – April 2011)

  • 16 newly-diagnosed patients with GBM enrolled between May 2007 and November 2009, 11 (69%) are still alive after a median time of 30 months
  • Six (38%) continue to show no tumor progression for more than two years without disease progression
  • Overall two-year survival for patients treated with ICT-107 was 80%, compared to historical rates for overall survival on standard treatment of 26% in all GBM and 38% in GBM patients whose tumor is completely resected (Stupp et al, NEJM 2005)
  • Median overall survival has not yet been reached
  • Median Progression-Free Survival (PFS) for patients receiving the cancer vaccine was 16.9 months, comparing favorably with historical PFS of 6.9 months for patients receiving standard treatment, and two-year estimated PFS for vaccine-treated patients was 44%
  1. Multiple Antigen vs. Single Antigen vs. Whole Cancer Vaccines

Multiple Antigens/Cancer Stem Cells (CSCs): Immunocellular

ICT-107 targets multiple antigens (gp100, Trp-2, Her-2/neu, MAGE-1, AIM-2, IL-13aR2).  ImmunoCellular selected epitopes that stimulate dominate T-Cells including Trp-2 (high CSC Expression) and IL-13Ra2 (high expression in bulk tumor cells).

Platform Strength: Reduced ability of cancer cells to mutate (dendritic cells sensitized with multiple antigens targeting both cancer stem cells and bulk tumor cells).

Single Antigen: Celldex

Celldex’s APC Targeting Technology™ uses human monoclonal antibodies (mAbs) to deliver a disease target or antigen directly to APC (antigen presenting cells). mAbs are specific for receptors located on the surface of these APCs which are known to be entry portals for antigen processing pathways.

Lead clinical development program, CDX-110, is an immunotherapy that targets the tumor specific molecule called EGFRvIII, a functional variant of the epidermal growth factor receptor (EGFR), a protein that has been well validated as a target for cancer therapy.

Potential Platform Vulnerability: Cancer cell mutation

Whole Tumor Vaccines: Northwest Biotherapeutics

The Company’s platform technology, DCVax®, uses a patient’s own dendritic cells. The dendritic cells are extracted from the body, loaded with tumor biomarkers or ‘‘antigens’’, thereby creating a personalized therapeutic vaccine.

The company’s lead product candidate is DCVax®-Brain which targets GBM. DCVax®-Brain has entered a Phase II FDA-allowed clinical trial.

Potential Platform Vulnerability: Antigens not optimized; not powerful enough to maintain tumor response

  1. Cost of Goods Sold (COGS)

Immunocellular generates 20 doses from one outpatient apheresis procedure (reduced cost of goods in comparison to Dendreon’s PROVENGE®) and employs cryopreservation technology to preserve product for several years.

Dendreon’s PROVENGE® requires 3 doses given at approximately 2-week intervals by intravenous infusion; each dose of PROVENGE® is preceded by a standard leukapheresis procedure approximately 2 to 3 days prior to the infusion date.



News Summary Clinical & Regulatory:

Caris Life Sciences, Inc. presented clinical data that validated the potential diagnostic impact of new biomarker profiles in combating breast cancer. These findings further support the diagnostic value of personalizing cancer treatment based on a tumor’s unique genetic make-up. The data was derived by profiling cancer patients through the Caris Target Now(TM) evidence-based molecular profiling service, which examines a patient’s tumor and provides a customized tumor-specific biomarker analysis, which is then matched with treatment guidance published by the world’s most respected cancer researchers. The study also showed that equivocal HER2 results either by IHC or FISH cannot be resolved by microarray analysis due to poor inter-assay agreement. HER2 over-expression occurs in approximately 15-20% of patients with breast cancer and is associated with aggressive disease and decreased survival. The Caris Target Now molecular profiling service matches information from the individual tumor’s genetic profile with data included in the nearly 100,000 published clinical studies reviewed by Caris’ evidence team. Caris Target Now then provides a simple report indicating which available chemo, biologic, and hormone therapies are most likely to be effective and those that are likely to be ineffective. Caris Target Now emerged last year as the world’s most comprehensive and actionable tumor profiling service, with nearly 20,000 patients profiled to date.

 

Roche Holding AG announced topline results of first randomized trial of trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer. The Phase II trial, known as TDM4450g, compar trastuzumab emtansine (T-DM1) single agent to the combination of Hercep (trastuzumab) and chemotherapy (docetaxel) in previously untreated patients. The results showed that patients treated with trastuzumab emtansine (T-DM1) in this study lived significantly longer with their disease under control (PFS) and experienced fewer side effects typical of chemotherapy. Data from the TDM4450g study will be submitted for presentation at a future medical congress. An earlier analysis of this study presented at the 35th Congress of the European Society of Medical Oncology (ESMO) in 2010 showed encouraging results in tumour shrinkage (overall response rate ORR) in patients with a minimum of 4 months of follow-up. In addition, the study showed that trastuzumab emtansine (T-DM1) significantly reduced the burden of typical side effects associated with conventional chemotherapy.

 

Precision Therapeutics, Inc. announced that the launch of a new product line, BioSpeciFx(R), will help further the personalization of cancer treatments. BioSpeciFx(R) is composed of carefully selected sets of well validated and clinically useful biomarker tests that identify critical molecular targets within a patient’s cell. By using the information generated by BioSpeciFx(R) in combination with Precision’s sophisticated drug response marker ChemoFx(R), physicians may gain a more complete understanding of a patient’s tumor. When combined, both products offer a complementary sum of information which will enable physicians to look at both the relevant molecular targets as well as the synergistic activity of drug combinations on the entire cell. BioSpeciFx(R) provides proteomic and genomic information, while ChemoFx(R) takes into account all of the functional characteristics of a tumor including those not captured by biomarker testing, providing both sensitivity and resistance information.

 

CEL-SCI Corp. has received approval to begin enrollment of patients in its Phase III clinical trial of Multikine(R) in India from the Directorate General of Health Services Office of Drug Controller General (India). The global Phase III trial for Multikine was started in the United States in late December 2010. CEL-SCI expects to commence the trial in other countries around the world within the next 30-60 days. Multikine is the Company’s flagship immunotherapy developed as a first-line standard of care in the treatment of head and neck cancer. CEL-SCI’s Phase III clinical trial is an open-label, randomized, controlled, multi-center study designed to determine if Multikine administered prior to current standard of care (surgery plus radiotherapy or surgery plus concurrent chemo radiotherapy) in previously untreated subjects with Advanced Primary Squamous Cell Carcinoma of the Oral Cavity/Soft Palate (Head and Neck cancer) will result in an increased overall rate of survival, versus the subjects treated with standard of care only. CEL-SCI’s 880 patient Phase III trial is expected to be the largest clinical study of head and neck cancer ever conducted. It is also the first trial in which immunotherapy will be administered before any other traditional means of care are attempted. This is significant because conventional cancer therapy weakens the immune system and likely compromises the benefits of immunotherapy. Phase II clinical trials of Multikine demonstrated that the product was safe and well-tolerated and eliminated tumors in 12% of the subjects less than a month into treatment. The Multikine treatment regimen was also shown to kill, on average, about half of the cancer cells in the subjects’ tumors before the start of standard therapy. Follow-up studies of subjects enrolled in Phase II trials showed a 33% improvement in the survival rate of those treated with Multikine at a median of three and a half years following surgery. The U.S. Food and Drug Administration granted orphan drug status to Multikine in the neoadjuvant therapy of patients with squamous cell carcinoma of the head and neck.

 

Marina Biotech, Inc. announced the initiation of patient dosing in the Dose Escalation Phase of its START-FAP (Safety and Tolerability of An RNAi Therapeutic in Familial Adenomatous Polyposis) clinical trial with CEQ508. Marina Biotech’s Phase 1b/2a trial is an open-label, escalating-dose study of single daily doses of CEQ508 and will be conducted as a single center study in Boston, Massachusetts. The first cohort comprised of three patients will be administered the starting dose of 1×10(8) colony forming units (cfu)/day. The study is primarily designed to evaluate the safety and tolerability of CEQ508 in patients with Familial Adenomatous Polyposis (FAP) after 28 days of daily, oral dosing. The trial is also intended to provide data on beta-catenin biomarker changes pre- and post-treatment and pharmacokinetic data related to the gastrointestinal coverage of CEQ508. The Dose Escalation Phase consists of 12 patients in four dose escalating cohorts; two patients in the first dosing group have been enrolled.

 

Progen Pharmaceuticals Limited announced that the PG11047 Phase Ib 7 arm, 172 patient combination study has completed patient enrolment. This Study (number 47-01-002) is entitled ‘A Phase I Open label, Multicentre, Dose Escalation Study to determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT), Safety and Pharmacokinetics of PG11047 when used in Individual Combinations with Gemcitabine or Docetaxel or Bevacizumab or Erlotinib or Cisplatin or 5- Flurouracil or Sunitinib in Patients with Advanced Solid Tumours or Lymphoma. This is a significant study with 172 patients enrolled across 12 US Oncology sites. The Primary Objective of this study was to determine the MTD and DLT of PG11047 when used in combination with other approved anti-cancer products and also to establish the recommended dose for future studies. The Secondary Objective of the study was to establish the pharmacokinetics of PG11047 when used in each of the combinations assessed and to observe patients for any evidence of anti-tumour activity. The patient data will now be analysed and a Clinical Study Report is expected in Third Quarter 2011. PG11047 is a novel, conformationally restricted analog of the natural polyamine, spermine that lowers cellular endogenous polyamine levels and competitively inhibits natural polyamine functions leading to cancer cell growth inhibition. The company has previously announced that it is planning to divest the cell proliferation and epigenetic assets including PG11047 as they are not part of its core program or focus.

 

AstraZeneca PLC announced that the U.S. Food and Drug Administration (FDA) approved the orphan drug vandetanib for the treatment of medullary thyroid cancer that cannot be removed by surgery or that has spread to other parts of the body. Vandetanib is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable (non-operable) locally advanced or metastatic disease. The use of vandetanib in patients with indolent, asymptomatic or slowly progressing disease should be carefully considered because of the treatment-related risks. Vandetanib is the only medicine to receive FDA approval specifically for use in patients with advanced medullary thyroid cancer and is the first treatment that AstraZeneca has developed and brought to market under orphan drug designation in the US. The approval of vandetanib is based on the results of the ZETA study, a Phase III, double-blind trial that randomized 331 patients with unresectable locally advanced or metastatic medullary thyroid cancer to vandetanib 300 mg (n=231) or placebo (n=100). In the study, patients randomized to vandetanib showed a statistically significant improvement in progression-free survival (PFS) when compared to those randomized to placebo (Hazard Ratio [HR]=0.35; 95% Confidence Interval [CI]=0.24-0.53; p<0.0001). This difference reflects a 65% reduction in risk for disease progression. Median progression-free survival was 16.4 months in the placebo arm and at least 22.6 months in the vandetanib arm. At the primary PFS analysis, no significant overall survival difference was noted. QT prolongation, Torsades de pointes, and sudden death are included in the boxed warning for vandetanib. The most common adverse drug reactions (>20%) seen in the ZETA trial with vandetanib were diarrhea (57%), rash (53%), acne (35%), nausea (33%), hypertension (33%), headache (26%), fatigue (24%), decreased appetite (21%), and abdominal pain (21%). A Risk Evaluation and Mitigation Strategy (REMS) is required for vandetanib due to the risks of QT prolongation, Torsades de pointes, and sudden death. Only prescribers and pharmacies who are certified through the vandetanib REMS program, a restricted distribution program, will be able to prescribe and dispense vandetanib. AstraZeneca will work to make vandetanib available to patients as soon as possible. Vandetanib will be dispensed exclusively through the pharmacy business unit of Biologics Inc., an integrated oncology management company.

 

Seattle Genetics Inc. announced that data from a case series of Hodgkin lymphoma patients receiving brentuximab vedotin (SGN-35) following allogeneic stem cell transplant were presented in an oral session at the European Group for Blood and Marrow Transplantation (EBMT) Annual Meeting in Paris, France. Brentuximab vedotin is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of Hodgkin lymphoma. This is the first report of data from brentuximab vedotin in Hodgkin lymphoma patients who relapsed following allogeneic transplant. Patients in the company’s pivotal Hodgkin lymphoma trial had all relapsed following autologous transplant, but none had received an allogeneic transplant. Patients relapsing following allogeneic transplant represent a particularly difficult therapeutic challenge. Key findings from this case series of 25 post-allogeneic transplant patients include: — 50% of patients achieved an objective response including 38% complete remissions; an additional 42% of patients had stable disease.

— Median progression-free survival (PFS) was 34 weeks; median overall survival had not been reached. — The median time to objective response was 8.1 weeks and patients received a median of 8 cycles of therapy; five patients remain on treatment. — Brentuximab vedotin administration was associated with manageable adverse events, with the most common being cough, fatigue, fever, nausea and peripheral sensory neuropathy. — The most common Grade 3 or higher adverse events were neutropenia, anemia, fatigue and fever. The case series comprises data from Hodgkin lymphoma patients who relapsed following allogeneic stem cell transplant that were enrolled in one of three multicenter, open label clinical trials of brentuximab vedotin. Patients received 1.2 or 1.8 milligrams per kilogram of brentuximab vedotin every three weeks. The median age of patients was 32 years. Enrolled patients had received a median of five prior therapeutic regimens, including 76% who had a prior autologous stem cell transplant.

 

Asuragen, Inc. announced the launch of Inform(TM)Thyroid, a panel of molecular markers used on Fine Needle Aspirates (FNA) of thyroid nodules to aid physicians in the management of thyroid cancer. The FNAs are analyzed in Asuragen’s CAP accredited CLIA Laboratory.

 

Avila Therapeutics, Inc. announced that it has successfully completed two Phase 1a clinical studies for AVL-292, its orally-available, selective inhibitor of Bruton’s tyrosine kinase (Btk). Avila presented summary results from the first-in-human study, AVL-292-001, at the Keystone Symposium on Molecular and Cellular Biology: Evolving Approaches to Early-Stage Drug Discovery. The study AVL-292-001 was a double-blind, placebo-controlled, single ascending dose study in healthy volunteers and in this study AVL-292 demonstrated favorable safety, tolerability, and pharmacokinetics. In addition, the trial used Avila’s unique covalent probe technology to assess the quantitative relationship among dose level, systemic exposure and occupancy of the target by AVL- 292. This combination of analyses provides a powerful and rigorous understanding of AVL-292 action at the molecular level and serves as a rational guide to future clinical development. Clinical development of AVL-292 has been supported, in part, through an alliance with The Leukemia & Lymphoma Society (LLS). AVL-292 is a novel, orally available, covalent drug that targets Bruton’s tyrosine kinase (Btk). Inhibition of Btk is a promising new approach to treatment of diseases that are driven by B cells, including certain cancers and autoimmune diseases. AVL-292 selectively and covalently binds to Btk to inactivate and silence its activity. This unique mechanism of action confers greater target selectivity and a longer duration of action than is typical of conventional small molecule drugs. In preclinical studies, AVL-292 selectively and potently inhibited Btk and B cell receptor signaling in vitro and was efficacious in a variety of animal disease models. AVL-292 is in clinical development and has successfully completed two Phase 1a clinical studies to date. AVL-292 achieved statistically significant levels of target occupancy at all dose levels, with >80% Btk target site occupancy achieved at doses as low as 1.0 mg/kg. AVL-292 was well-absorbed with good systemic exposure and demonstrated a dose-proportional pharmacokinetic profile across all dose levels (ranging from 0.5 to 7.0 mg/kg) with low inter-subject variability. AVL-292 was shown to be generally safe and well tolerated.

 

Progen Pharmaceuticals Limited announced that it had presented new preclinical data on its dual angiogenesis and heparanase inhibitor, PG545, at the American Association for Cancer Research meeting being held in Oriando, Florida. The meeting brings together almost 20,000 participants from around the world to discuss new and significant advances in the causes, diagnosis, treatment and prevention of cancer. The data presented shows that PG545 slows solid tumour growth and potently inhibits the development of spontaneous lung metastasis in a model of breast cancer. Moreover, blockade of metastasis is linked with significantly improved overall survival. PG545 is currently being evaluated in cancer patients in a Phase I clinical trial in Australia.

 

Axelar AB announced positive results from the completed first part of the combined phase I/II clinical trial, evaluating AXL1717 as a new treatment for solid tumors. The study has successfully reached its primary endpoint, identifying the recommended phase II dose as well as provided evidence that AXL1717 is safe and tolerable. Furthermore, data also supports the company’s strategy to target AXL1717 in patients with squamous non-small cell lung cancer. Results will be presented later 2011. In the ongoing study, AXL1717 has been tested in total of more than 45 patients. The now completed first part of the study with a total of 35 patients, consisted of a single-day dosing as well as a multi dosing part. The study has been amended to a phase II design. AXL1717 is now tested for 28 days BID (twice daily dosing) in two cycles with 14 days interval in order to confirm the phase II regimens and explore the possible anti-tumor effects. A phase II program is expected to start late 2011.

 

Circadian Technologies Ltd. announced its anti-cancer therapeutic, VGX-100, significantly inhibits tumour growth and spread in a variety of different mouse models of human cancer including lung, ovarian and prostate cancer. Subject to the successful completion of the animal safety/toxicology studies, Circadian intends to file an Investigational New Drug application with the US Food And Drug Administration in the third quarter of 2011 in order to begin human clinical trials of VGX-100.

 

Semafore Pharmaceuticals, Inc. announced encouraging preclinical results for its lead product candidate, SF1126, in certain B-cell malignancies. The data demonstrated that the therapeutic effects of SF1126 are superior to a delta isoform-selective PI3K inhibitor (CAL-101) both alone and in combination with rituximab in two diffuse large B-cell lymphoma (DLBCL) cell lines. These data, generated through a collaboration with Dr. Daruka Mahadevan of Arizona Cancer Center, were presented during a late-breaking poster session at the 102nd Annual Meeting of the American Association for Cancer Research (AACR) in Orlando, Florida. SF1126 is a novel peptidic prodrug that converts to LY294002, one of the most widely studied small molecule inhibitors of multiple, cancer-specific kinase targets, including all Class I phosphatidylinositol 3-kinase (PI3K) isoforms, mammalian target of rapamycin (mTOR), Pim-1, DNA-activated protein kinase (DNA-PK), and polo-like kinase 1 (PLK1).

 

TapImmune, Inc. anticipates that an IND for the first Phase I study in program to develop a vaccine against HER-2/neu breast cancer will be filed soon. The technology entering the clinic targets a novel set of HER-2/neu antigens discovered in breast cancer patients with pre-existent immunity to these antigens (Clinical Cancer Research 16[3]:825-34, 2010). This technology complements TapImmune’s TAP technology that the company envision as part of a final vaccine product. This technology is currently completing preclinical development. Currently, Herceptin(R) (trastuzumab: an intravenously delivered monoclonal antibody) is used in the treatment of HER-2/neu breast cancer. Ongoing collaborative research, on a new smallpox vaccine, will select the most potent peptide antigens against the smallpox virus for combination with its TAP technology. In preclinical studies (Plos Pathogens 1: 289-98, 2005) TAP technology improved the efficacy of a vaccinia virus vaccine by over a hundred fold. TapImmune believes that this approach provides the potential for development of a vaccine against smallpox that has broader application, is more cost effective and has a better shelf-life than existing viral-based products. TapImmune plans to evaluate its TAP technology for improving the efficacy of vaccines designed to combat a range of additional viral threats in the biodefense and infectious disease field. To expand its technology platform TapImmune also plans to enter additional technology collaborations for the development of DNA plasmid expression vectors that can deliver TAP genes into target cells.

 

Keryx Biopharmaceuticals Inc. announced that two posters on KRX-0401 (perifosine) were presented at the 102nd annual meeting of the American Association for Cancer Research currently ongoing at the Orange County Convention Center in Orlando, Florida. Perifosine, the company’s novel, potentially first-in-class, oral anti-cancer agent that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway, is currently in Phase 3 clinical trials for refractory advanced colorectal cancer and multiple myeloma. Both of these Phase 3 programs are being conducted under Special Protocol Assessment (SPA) agreements with the FDA, and with Fast Track designations obtained for both indications. Perifosine is also in Phase 1 and 2 clinical development for several other tumor types. Perifosine showed single agent anti-proliferative activity in a variety of gastric cancer cell lines. In 8/13 cell lines resistant to 5-FU, perifosine showed a synergistic antiproliferative activity with 5-FU. In 72% of cell lines, high basal levels of pAkt were detected. Treatment with perifosine reduced tumor growth in nude mice inoculated subcutaneously with the YCC 2 gastric cancer cell line. Finally, an MTT based microarray analysis was performed to identify pharmacogenomic classifiers for synergy in 5-FU resistant cell lines. Perifosine demonstrated antitumor activity in several gastric cancer cell lines. Furthermore, perifosine enhanced the antitumor activity of 5-FU including 5-FU resistant cell lines. 5-FU is the active metabolite of the pro-drug Xeloda(TM) (capecitabine), which is approved for the treatment of metastatic colorectal cancer and breast cancer in the U.S., as well as advanced gastric cancer in certain countries outside of the U.S. Pro-apoptotic TRAIL receptors present on tumor cells are known to represent a potential pharmaceutical target for cancer treatment. Perifosine stimulated the expression of pro-apoptotic TRAIL receptors on the multiple myeloma KMS-11 cell line, substantially reduced the levels of phosphorylated Akt and significantly enhanced the sensitivity of these cells for trail induced apoptosis. The same molecular effects were noted in the non-Hodgkin lymphoma cell line SU-DHL-4V. In this TRAIL resistant cell line, perifosine treatment substantially enhanced the cytotoxicity of TRAIL treatment to similar levels observed in the TRAIL sensitive multiple myeloma cell line. The synergistic activity was confirmed in NOD/SCID mice xenograft models, where perifosine induced a down-modulation of Akt expression as well as TRAIL receptor upregulation in tumor cells and tumor endothelial cells.

 

Telik Inc. presented data at the 102nd American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida on a group of second generation analogs of ezatiostat, the most clinically advanced product in development at Telik. Ezatiostat is the first inhibitor of glutathione-S-transferase P1-1 (GST P-1), a validated enzyme target in Myelodysplastic Syndrome (MDS), to successfully complete a Phase 2 clinical trial. The efficacy and tolerability observed with ezatiostat in several Phase 1 and Phase 2 clinical trials supported the initiation of the analog program to identify potential follow-on drug candidates. The structure-activity relationships for the most compelling of these analogs are presented in the AACR poster, entitled Synthesis and Biochemical Characterization of Novel Analogs of Ezatiostat Hydrochloride (TELINTRA(R), TLK199) by Danying Cai et al. A series of diacid ezatiostat analogs bearing different substituents on the cysteinyl sulfur were synthesized using computer aided drug design and TRAP(R), a proprietary drug discovery technology, to improve the inhibitory potency and selectivity for the target enzyme GST P1-1. Substitutions resulted in a 30- to 130-fold improvement in vitro potency against GST P1-1 and 3- to 10-fold higher selectivity relative to other isoforms. Select ezatiostat analogs were evaluated for toxicity as well as for acceleration of recovery of neutrophil levels in a standard preclinical model of 5-fluorouracil chemotherapy-induced neutropenia. The compounds were well-tolerated when administered at doses up to 200 mg/kg and, like ezatiostat, led to a significantly accelerated recovery in the 5-FU-induced neutropenia model. Ezatiostat treatment has been shown to cause a clinically significant and sustained reduction in red-blood-cell transfusions, transfusion independence and multilineage hematologic improvement responses in patients with MDS.

 

Oncothyreon Inc. announced enrollment of the first patient in a Phase 2 trial of PX-866 in patients with glioblastoma multiforme that has recurred during or following primary therapy. PX-866 is a small molecule compound designed to inhibit the activity of phosphatidylinositol-3-kinase (PI-3K), a component of an important cell survival signaling pathway. The Phase 2 trial is being conducted at 7 Canadian centers by the NCIC Clinical Trials Group (NCIC CTG), Queen’s University in Kingston, Canada. The trial will enroll up to 30 patients whose brain tumor is in first relapse during or following primary therapy. The primary endpoint of this single-arm screening trial is a combination of objective response rate and early progression. PX-866 is an inhibitor of the PI-3K/PTEN/AKT pathway, a critical cell signaling pathway that is activated in many types of human cancer. Aberrant activation and regulation of PI-3K is implicated in a large proportion of human cancers, where it leads to increased proliferation and inhibition of apoptosis (programmed cell death). Results from a single-agent Phase 1 open-label, dose escalation study of PX-866 in patients with advanced metastatic cancer presented at the American Society of Clinical Oncology earlier this year demonstrated that PX-866 was well tolerated using both an intermittent and continuous (daily) dosing schedule. Additional data from the Phase 1 trial presented at the EORTC/NCI/AACR meeting in Berlin on November 18, 2010 demonstrated that 8 of 19 evaluable patients treated with continuous dosing achieved stable disease as their best response.

 

Ariad Pharmaceuticals Inc. announced results of preclinical studies on ponatinib, its investigational pan-BCR-ABL inhibitor, showing potent inhibition of all four members of the fibroblast growth factor receptor (FGFR) family of tyrosine kinases that are abnormally expressed in multiple cancers. Recent research has established that FGF receptors 1 to 4 are activated through multiple mechanisms in certain solid tumors and represent promising targets for antitumor therapy. The new data on ponatinib demonstrate potent activity against a broad range of tumor cells activated by all four FGFRs, in vitro and in vivo. In a panel of 14 cell lines representing multiple different tumor types including endometrial, bladder, gastric, breast, lung and colon cancer, ponatinib potently and selectively inhibited FGFR-mediated signaling and cell growth. Four other tyrosine kinase inhibitors with FGFR inhibitory activity that are in clinical development were substantially less active, and none potently blocked all four FGF receptors. In mouse models of FGFR-driven tumors, daily oral dosing of ponatinib reduced tumor growth and inhibited signaling in all 3 FGFR-driven models examined. Ponatinib reduced tumor growth by 80% in mouse models of bladder and endometrial cancers and induced tumor regression in a model of gastric cancer. Potency was similar to that previously observed in BCR-ABL-driven models of chronic myeloid leukemia (CML). Importantly, the Phase 1 trial of ponatinib in CML shows that plasma concentrations of ponatinib required for inhibition of all four FGFRs can be sustained at well-tolerated doses in patients.

 

Exiqon A/S announced positive results in the company’s development of a diagnostic test for early detection of colorectal cancer in blood. The results were revealed during an oral presentation at the annual American Association for Cancer Research (AACR) meeting in Florida, USA. In a multicenter study, Exiqon has demonstrated the ability of the company’s proprietary miRCURY LNA(TM) Universal RT microRNA PCR platform to robustly detect miRNA biomarkers associated with the presence of colorectal cancer based on less than 0.2 ml blood. The objective for the first phase of the early detection of colorectal cancer program was to identify candidate miRNA biomarkers in plasma samples from stage II/III colorectal cancer patients and age- and gender-matched colonoscopy-verified healthy controls. A genome wide screen in blood plasma profiled 730 individual miRNAs from 50 stage II cancers and 50 matched controls. The results were used to develop a candidate panel of miRNAs detectable in less than 0.1 ml plasma. In the second phase of the program, the candidate panel of miRNAs was profiled in a study set of 227 stage II/III colorectal cancer patients and matched controls. The results demonstrated that using a simple miRNA signature derived from plasma obtained under standard clinical conditions it is possible to detect colorectal cancer. In the study, including samples from patients with proven colorectal cancer and matched healthy subjects from five Danish hospitals, the biomarker signature had a sensitivity and specificity for cancer of 75% and 80%, respectively, easily fulfilling the requirement for a commercial test. Exiqon has begun the next phase which includes final assay development and validation of the biomarker signature in a larger study cohort of more than 3,000 patient/control samples. Exiqon plans to publish the results of the validation study before year end.

 

Eli Lilly & Co. announced results from two preclinical studies of molecules that target genetic mutations and disable specific signaling pathways that can lead to cancer. The studies evaluated two unique molecules a JAK2 inhibitor and a Hedgehog inhibitor with results presented during the American Association for Cancer Research (AACR) 102nd Annual Meeting in Orlando, Fla. Signaling pathways within cells regulate genes that underlie crucial biological processes including cell division, embryonic development and immunity. When these networks of proteins misfire, many types of cancer can result. The company showed how these pipeline molecules target out-of-control signaling pathways. The company is focused on developing therapies tailored for an individual patient’s needs such as a cancer treatment that targets a specific genetic mutation. New Small Molecule Therapeutics mini-symposium suggested that the investigational compound LY2784544, a small-molecule JAK2 inhibitor, blocks a specific, difficult-to-isolate, signaling pathway that can lead to the development of cancer cells. Specifically, company’s researchers chose to study inflammatory breast cancer (IBC) cells because these cells support their own survival by secreting chemicals known as growth factors, which allow them to break away from the primary tumor, multiply and then cluster together into tumor spheres ultimately metastasizing, or spreading. The company scientists focused on a growth factor called IL-6, which latches onto receptors on the surface of cells and triggers the IL-6–JAK–STAT3 signaling pathway, promoting formation of the deadly IBC cell clusters by activating the STAT3 protein, which then turns on the genes that encourage IBC cells to stick together. Researchers hypothesized that short-circuiting the IL-6–JAK–STAT3 pathway could prevent the formation of tumor cell clusters. The scientists first cultured the tumor spheres in medium containing IL-6. As expected, IL-6 activated STAT3, the cells proliferated, and the tumor spheres grew. Furthermore, expression of IL-6 by the spheres themselves increased by 50-fold; and secretion of intracellularly produced IL-6 activated STAT3, and prevented cell death in the tumor spheres. But when company’s JAK2 inhibitor was added to the medium containing the tumor spheres, the scientists found that it inhibited STAT3 activation in a dose-dependent manner and that blocking this signaling pathway induced cell death in the tumor spheres. The IL-6–JAK–STAT3 pathway may serve as a ‘molecular signature’ of IBC and as a potential therapeutic target. The company’s JAK2 inhibitor is currently being evaluated in Phase I clinical trials for the treatment of myeloproliferative neoplasms, or diseases of the blood and bone marrow, called polycythemia vera, essential thrombocythemia and myelofibrosis. Scientists have identified an orally administered anti-cancer agent, LY2940680, which, in preclinical studies, disrupted the abnormal signaling of a key regulator of embryonic cell development. This novel molecule has been shown to affect a cancer cell signaling pathway initiated by the Hedgehog (Hh) protein, which is essential for regulating normal cell differentiation and proliferation. Abnormal Hh signaling has been implicated in several types of cancer, including brain, lung, breast, prostate and skin cancers. Abnormal Hh pathway activation can result from genetic mutations in the pathway’s protein components. One such protein component, known as Smoothened (Smo), is a key regulator of the Hh signaling pathway and is seen as a potential target for therapies aimed at treating cancer by halting abnormal Hh signaling. Scientists have identified that company’s Hedgehog inhibitor is a small molecule antagonist of Smo, binding to it and inhibiting Hh signaling in a human medulloblastoma tumor cell. (Medulloblastoma is the most commonly diagnosed form of brain tumor in children, but is rare in adults. In addition, when the compound was orally administered to transgenic mice that spontaneously develop medulloblastoma, it improved animal survival. The company’s Hedgehog inhibitor is currently being studied in Phase I clinical trials for solid tumors.

 

OncoGenex Pharmaceuticals, Inc. announced that preclinical data utilizing their pipeline compound OGX-427 was presented at the AACR 102nd Annual Meeting 2011. The study demonstrated the ability of OGX-427 to inhibit Heat Shock Protein 27 (Hsp27), a cell-survival protein believed to play an important role in the proliferation of castrate resistant prostate cancer (CRPC) and resistance to standard therapies. Hsp27, expressed in prostate cancer and a variety of other malignancies, can be induced by cell stress such as chemotherapy, radiation therapy, and hormone therapy. Molecular chaperones that are heat shock proteins such as Hsp27 act to repair the damage of misfolding of cell structures that can occur when a cell is stressed, thereby enhancing the ability of cancer cells to survive. The goal of this study was to test the ability of OGX-427, a second-generation antisense therapy, and other mechanisms (siRNA and proteasome inhibition MG132) in silencing the effects of Hsp27. The study showed that OGX-427 inhibits Hsp27 and therefore a cell survival process called autophagy, to increase intracellular unfolded protein burden and cause prostate cancer cell death. These pre-clinical data further support the current OGX-427 development plan in prostate and bladder cancers: An Investigator-sponsored Phase 1 clinical trial evaluating OGX-427 administered directly into the bladder in patients with superficial bladder cancer, which was initiated in August 2009; An investigator-sponsored, randomized Phase 2 clinical trial evaluating OGX-427 when administered as monotherapy to patients with castrate-resistant prostate cancer. This trial will enroll approximately 72 patients and was initiated in September 2010; A planned Phase 2 clinical trial of OGX-427 in approximately 180 patients with metastatic bladder cancer, which is planned to initiate in the second half of 2011.

 

Aeterna Zentaris Inc. announced that two posters on its lead anticancer agent, perifosine, were presented at the 102nd annual meeting of the American Association for Cancer Research currently held at the Orange County Convention Center in Orlando, Florida. Poster #1965: Entitled, “Antitumor activity of novel Akt inhibitor, perifosine in gastric cell lines”,Tae Soo Kim, Hyo Song Kim, Bo Ram Kwan, Chan Hee Park, Hei-Cheul Jeung, Woo Ick Jang, Juergen Engel, Hyun Cheol Chung, Jae Kyung Roh, Sun Young Rha. Results: Perifosine showed single agent anti-proliferative activity in a variety of gastric cancer cell lines. In 8/13 cell lines resistant to 5-FU, perifosine showed a synergistic antiproliferative activity with 5-FU. In 72% of cell lines, high basal levels of pAkt were detected. Treatment with perifosine reduced tumor growth in nude mice inoculated subcutaneously with the YCC 2 gastric cancer cell line. Finally, an MTT based microarray analysis was performed to identify pharmacogenomic classifiers for synergy in 5-FU resistant cell lines. Conclusions: Perifosine demonstrated antitumor activity in several gastric cancer cell lines. Furthermore, perifosine enhanced the antitumor activity of 5-FU in parts of the cell lines – including 5-FU resistant cell lines. 5-FU is the active metabolite of the prodrug Xeloda, which is approved for the treatment of advanced gastric cancer in many countries including Japan and Korea. Poster #640: Entitled “The Akt inhibitor Perifosine strongly enhances the antitumor and antivascular activity of CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)”, Arianna Giacomini, Silvia L. Locatelli, Marco Righi, Loredana Cleris, Paolo D. Longoni, Marco Milanesi, Maura Francolini, Michele Magni, Massimo Di Nicola, Alessandro M. Gianni, Carmelo Carlo-Stella. Results: Pro-apoptotic TRAIL receptors present on tumor cells are known to represent a potential pharmaceutical target for cancer treatment. Perifosine stimulated the expression of pro-apoptotic TRAIL receptors on the multiple myeloma KMS-11 cell line, substantially reduced the levels of phosphorylated Akt and significantly enhanced the sensitivity of these cells for trail induced apoptosis. The same molecular effects were noted in the non-Hodgkin lymphoma cell line SU-DHL-4V. In this TRAIL resistant cell line, perifosine treatment substantially enhanced the cytotoxicity of TRAIL treatment to similar levels observed in the TRAIL sensitive multiple myeloma cell line. The synergistic activity was confirmed in NOD/SCID mice xenograft models, where perifosine induced a down-modulation of Akt expression as well as TRAIL receptor upregulation in tumor cells and tumor endothelial cells. Conclusion: Perifosine markedly enhanced the antitumor activity of the cellular TRAIL based treatment and was able to overcome TRAIL resistance both in vitro and in vivo. The results are in line with other studies demonstrating the synergistic effects of perifosine with cytotoxic drugs, including bortezomib and 5-FU.

 

Lorus Therapeutics Inc. announced the presentation of new data for its lead small molecule anti-cancer drug candidate LOR-253 at the 102nd Annual Meeting of the American Association for Cancer Research (AACR), taking place April 2-6, 2011 in Orlando, Florida. The presentation includes preclinical results on the anticancer efficacy of LOR-253 in human lung cancer, as well as an overview of the ongoing Phase I clinical trial for LOR-253 in advanced or metastatic solid tumors. In the presentation, LOR-253 was shown to be a potent inhibitor of growth of non-small cell lung cancer (NSCLC), both in vitro and in animal models of human NSCLC. Anticancer activity of LOR-253 in lung cancer models was related to expression of the tumor suppressor gene KLF4, which is a cell growth regulator that is either turned off or expressed at very low levels in many cancer types. LOR-253 was highly active against NSCLC cells with low KLF4 levels, while normal lung cells and lung cancer cells with higher levels of KLF4 were less sensitive to LOR-253. Anticancer efficacy of LOR-253 in NSCLC models was associated with induction of KLF4 in a dose-response manner. The results demonstrate that KLF4 is an important mediator of LOR-253 anticancer activity in NSCLC, and suggest that KLF4 may be an important biomarker for antitumor response to LOR-253 in this cancer type. In addition, an overview of the design of the Phase I clinical study of LOR-253 in advanced or metastatic solid tumors was presented. This Phase I study is an open-label, dose-escalation investigation to determine the maximum tolerated dose and recommended Phase II clinical dose of LOR-253. Additional trial objectives include the safety profile, pharmacokinetics and antitumor activity of LOR-253. The Phase I clinical study, which is being conducted at Memorial Sloan-Kettering Cancer Center in New York, is currently enrolling patients.

 

Threshold Pharmaceuticals Inc. announced multiple preclinical presentations on its clinical stage hypoxia-activated prodrug, TH-302, at the American Association for Cancer Research (AACR) Annual Meeting, being held April 2 to 6, 2011, in Orlando, FL. Abstract 535, J.D.Sun et al., entitled Hypoxia-dependent in vivo activity of the hypoxia-activated prodrug (HAP) TH-302, demonstrates that TH-302 targets the hypoxic compartment of preclinical tumors selectively in vivo. Abstract 5054, J.D.Sun et al., entitled Hypoxia-activated prodrug TH-302 enhances antitumor activity of antiangiogenics in preclinical models, provides a translational rationale for combining TH-302 with antiangiogenics to increase the treatment benefit in not only the approved indications (RCC, HCC, GIST) but also other indications, such as NSCLC. Abstract 2648, F.Meng et al., entitled Pharmacological modulation of TH-302-mediated in vitro cytotoxicity, demonstrates that TH-302 activity may be modulated by pharmacological modulators of both select reductases and DNA damage and repair pathways.

 

ProStrakan Group PLC announced the availability of ABSTRAL(R) (fentanyl) sublingual tablets as the first rapidly-disintegrating tablet placed under the tongue for breakthrough cancer pain. The U.S. Food and Drug Administration (F.D.A.) approved ABSTRAL, an opioid analgesic, in January 2011 specifically for the management of breakthrough pain in cancer patients, 18 years of age or older, who are already receiving, and who are tolerant to, opioid therapy for their underlying persistent cancer pain. ABSTRAL is available only through an F.D. A mandated program, ABSTRAL REMS (Risk Evaluation and Mitigation Strategy). ABSTRAL is the only available analgesic that disintegrates quickly under the tongue. It offers an alternative therapeutic choice to patients and clinicians with a simple, patient-friendly and predictable way of delivering fentanyl transmucosally, while retaining the individualized dose titration aspects required for optimal treatment of breakthrough pain.

 

Curis Inc. announced the presentation of interim Phase II clinical data on Hedgehog pathway inhibitor vismodegib in patients with basal cell nevus syndrome (BCNS), which is also commonly referred to as Gorlin syndrome. This data was presented at the 102(nd) Annual Meeting of the American Association for Cancer Research being held in Orlando, Florida, April 2-6, 2011. This Phase II double blind, randomized placebo-controlled, two arm multicenter clinical study of vismodegib has enrolled forty-one BCNS patients from September 2009 to January 2011. It is designed to assess the safety and efficacy of 150 mg of daily oral vismodegib versus placebo. A Data Safety Monitoring Board (DSMB), tasked with reviewing the unblinded results from an interim analysis of 29 patients who completed an average of 6 months of drug treatment, recently recommended to end the placebo arm of the trial due to statistically significant differences between the two groups, in order for all of the patients enrolled in the trial to receive vismodegib treatment. The DSMB’s analysis revealed that vismodegib reduced the rate of new BCCs from an average of 1.74 BCCs per month in the placebo group to 0.07 in the vismodegib group (p=<0.0001). Vismodegib also reduced the size of existing BCCs (-24cm vs. -3cm placebo, cumulative diameter, p=0.006). Some patients achieved near complete remission with no BCC developing resistance during this period of time on trial.

 

Immunogen Inc. announced the reporting of the first data on the company’s IMGN853 product candidate for the treatment of ovarian cancer and other types of solid tumors. The presentations are being given at the 102(nd) Annual Meeting of the American Association for Cancer Research (AACR) in Orlando, FL. IMGN853 is designed to selectively target and kill cancer cells expressing folate receptor 1 (FOLR1). This target is over-expressed on most cases of ovarian cancer as well as on other carcinomas including types of non-small cell lung cancers. IMGN853 was found to be highly effective against human ovarian cancer tumors in preclinical testing. The AACR’s 2011 Program Committee recognized the abstract on the IMGN853 in vivo preclinical findings as scoring among the top 2% of abstracts for poster presentations. IMGN853 is a TAP compound, which means it consists of a tumor-targeting antibody with one of ImmunoGen’s highly potent cell-killing agents attached via an engineered linker. The antibody serves to target the TAP compound specifically to cancer cells, and the cell-killing agent serves to destroy these cells. The target for IMGN853 — FOLR1 – is robustly expressed on most ovarian cancers as well as on certain non-small cell lung cancers and other carcinomas. This is based on target quantification methods developed by ImmunoGen scientists; the design of IMGN853 has been optimized for its target – both in its antibody component and in the novel linker used to attach the highly potent payload to the antibody and control its release inside a cancer cell; and the IMGN853 product candidate has been found to be highly active against human ovarian cancer tumors in preclinical testing.

 

Immunogen Inc. disclosed the profile and first preclinical data for the Company’s novel IMGN529 product candidate for the treatment of B-cell malignancies including non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). This disclosure was made in conjunction with the 102(nd) Annual Meeting of the American Association for Cancer Research (AACR) taking place in Orlando, FL. IMGN529 consists of a CD37-targeting antibody that has notable anticancer activity with the Company’s potent cancer-cell killing agent, DM1, attached using its SMCC linker.

Currently, NHL is widely treated with the antibody product, rituximab (Rituxan(R)). A therapeutic or “functional” antibody, rituximab has anticancer activity and a favorable tolerability profile. To achieve better activity, however, rituximab often is used in combination with chemotherapy agents, which increases efficacy but can reduce tolerability. This has led a number of companies to try to develop more effective antibody therapies for the treatment of NHL that target CD20, like rituximab. ImmunoGen scientists sought to identify an alternative target which is as widely expressed on malignant B cells as CD20 and offers other beneficial properties. One advantage of this approach is that it allows a resulting product candidate to potentially be used both instead of CD20-targeting therapies and with them. CD37 met these criteria; however, it was known to be difficult to develop humanized antibodies to this target that also have potent anticancer activity. Numerous antibodies were successfully created by ImmunoGen scientists. These were then screened on multiple criteria, including intrinsic anticancer activity, to select the antibody used in IMGN529. The scientists also evaluated alternative ImmunoGen linkers and cancer-cell killing agents to select the SMCC-DM1 combination. This combination is best known for its use in trastuzumab-DM1 (T-DM1), which also contains a functional antibody.

 

Oncothyreon Inc. announced the presentation of preclinical data for ONT-10, a therapeutic vaccine directed at cancers expressing MUC1, and PX-866, its irreversible inhibitor of phosphatidylinositol 3-kinase (PI3K), at the American Association of Cancer Research meeting in Orlando, Florida. ONT-10 is a therapeutic vaccine targeting MUC1 which has been designed to stimulate both the humoral and cellular arms of the immune response. Results presented at the meeting demonstrated that administration of ONT-10 produced a robust antibody response in mice that was specific for human tumor MUC1. A strong cellular immune response directed to the target was also shown. ONT-10 blocked the growth of two different tumors expressing human MUC1 in murine models, with a high proportion of animals tumor free at the conclusion of the experiment. Additionally, the adjuvant component of ONT-10, PET-Lipid A, a fully synthetic toll like receptor 4 (TLR4) agonist discovered by Oncothyreon, was shown to have enhanced potency compared to the adjuvant monophosphoryl lipid A (MPL). PX-866 is an oral, small molecule compound designed to inhibit the activity of PI3K, a component of an important cell survival signaling pathway. Data presented at the meeting concerned the efficacy of PX-866 alone or in combination with either docetaxel or cetuximab in direct patient human tumor xenograft models (DPTM) of squamous cell carcinoma of the head and neck (SCCHN) developed by Dr. Antonio Jimeno’s laboratory at University of Colorado School of Medicine. These models maintain the histology of the tumor and are particularly suited to preclinical evaluation of novel cancer therapeutics. PX-866 was equal or superior to docetaxel in slowing tumor growth in two of four DPTM and equal or superior to cetuximab in each of four DPTM. The combination of PX-866 plus docetaxel was superior to single agent therapy in three of four DPTM, while the combination with cetuximab was superior to single agent therapy in two of four DPTM. The data were presented by Daniel W. Bowles, M.D., University of Colorado School of Medicine, Aurora, Colorado. ONT-10 is a therapeutic vaccine targeting MUC1, a tumor-associated antigen present on many types of human malignant tumors, including lung, breast, colorectal, prostate and ovarian cancer. ONT-10 contains a forty three amino acid antigen which is glycosylated; the attached sugars are expected to contribute to the stimulation of an immune response to the vaccine. The adjuvant in ONT-10 is PET Lipid A, a fully synthetic TLR4 agonist developed at Oncothyreon. Oncothyreon currently expects to file an Investigational New Drug application for ONT-10 in the third quarter of 2011 and to begin a Phase 1 clinical trial by late 2011. ONT-10 and PET Lipid A are fully owned by Oncothyreon. PX-866 is a pan inhibitor of the PI-3K/PTEN/AKT pathway, a critical cell signaling pathway that is activated in many types of human cancer. Aberrant activation and regulation of PI-3K is implicated in a large proportion of human cancers, where it leads to increased proliferation and inhibition of apoptosis (programmed cell death). Results from a single-agent Phase 1 open-label, dose escalation study of PX-866 in patients with advanced metastatic cancer demonstrated that PX-866 was well tolerated using both an intermittent and continuous (daily) dosing schedule. Additional data from the Phase 1 trial presented at the EORTC/NCI/AACR meeting in Berlin on November 18, 2010 demonstrated that 8 of 19 evaluable patients treated with continuous dosing achieved stable disease as their best response.

 

Cell Therapeutics, Inc. announced that the April 2011 edition of the peer reviewed journal, Leukemia & Lymphoma (April 2011; 52(4): 620–628) published results of a phase I/II clinical trial evaluating the effect of cyclophosphamide, pixantrone, vincristine, and prednisone (“CPOP”) in treating patients with aggressive non-Hodgkin’s lymphoma (“NHL”) who relapsed following initial therapy with cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (“CHOP”). In the CPOP regimen, pixantrone substitutes for doxorubicin (H) in the CHOP regimen. The study enrolled 35 patients in the phase I portion of the trial and 30 patients in the phase II portion of the trial. A major tumor response was reported for 80% and 73% of patients in phase I and II respectively, with 57% and 47% of the patients achieving a complete or unconfirmed CR. Median overall survival in the phase II portion of the trial was 17.9 months with four patients achieving notable long-term disease-free survival ranging from 55 to 77 months, despite in some cases having failed multiple prior regimens including stem cell transplantation. High response rates were also observed in the 43% of patients who had received prior rituximab as part of their front-line regimen (CHOP-R), with an ORR rate of 77% and CR rate of 54%. Myelosuppression was the most common toxicity. Side effects (grade 3/4) in phase I of the trial included febrile neutropenia (11%), grade 3/4 infections (3%), and cardiac failure (6%). In phase II of the trial, side effects (grade 3/4) included febrile neutropenia (20%), and cardiac failure (3%).

 


Corporate Finance:

ProMetic Life Sciences Inc. reported consolidated financial results for the year ended December 31, 2010. For the year, the company generated revenues of CAD 11.4 million compared to CAD 13.6 million for the year ended 31 December 2009. Delays in programs caused by both the regulatory process and strategic deals for two of major customers, Octapharma and Abraxis, impacted significantly on revenues in the second half. The company returned a net loss of CAD 11.3 million or CAD 0.03 per share (basic and diluted), as compared to a net loss of CAD 9.3 million or CAD 0.03 per share (basic and diluted) for year ended December 31, 2009. Analysing the increase in the annual loss of CAD 1.9 million from the previous year, CAD 1.3 million can be explained by the PRDT gain in 2009 not being repeated in 2010 and CAD 0.2 million associated with lower exchange gains in 2010.

Advaxis Inc. has filed a Shelf Registration in the amount of $3.45 million.

ImmunoCellular Therapeutics, Ltd. has filed a Shelf Registration in the amount of $18.09 million.

 


Mergers & Acquisitions:

SuperGen Inc. (NasdaqGS: SUPG) entered into a definitive agreement to acquire Astex Therapeutics Limited from Cambridge Enterprise Seed Funds, Apax Partners Worldwide LLP, Abingworth Bioventures III, Abingworth Bioventures II, Abingworth LLP and other shareholders in cash and  stock on April 6, 2011. Pursuant to the terms of the agreements, SuperGen will pay to Astex shareholders $25 million in cash, plus shares in SuperGen common stock representing 35% of the total post closing shares outstanding. Subsequently, SuperGen plans to pay deferred consideration in the amount of $30 million, to be paid in stock or cash at the discretion of the combined entity, over a period of 30 months. The combined entity will assume all outstanding incentive stock options of Astex Therapeutics Limited. SuperGen must pay Astex a termination fee of $6 million.

The combined entity to be named Astex Pharmaceuticals, Inc. The combined companyis expected to be listed on NASDAQ under the symbol ASTX. Under the new management structure, James S.J. Manuso, Chairman, Chief Executive Officer of SuperGen Inc., would become Chairman and Chief Executive Officer of Astex Pharmaceuticals, Inc., and Harren Jhoti, Chief Executive Officer of Astex Therapeutics Limited, would become President and a member of the Board of Directors of the combined entity. The Board of Directors of the combined entity would also include Peter Fellner as Vice Chairman, Walter Lack, Charles Casamento, Thomas Girardi, Allan Goldberg, Tim Haines and Ismail Kola. The transaction is subject to various customary closing conditions, including the approval of the issuance of the new SuperGen shares by the stockholders of SuperGen, U.S. and U.K. regulatory review clearance and shareholder approvals of SuperGen Inc. and Astex Therapeutics Limited, the absence of any order or injunction of a court of competent jurisdiction that prohibits the consummation of the transaction, the absence of certain governmental restraints, and  the performance in all material respects by each party of its obligations under the implementation agreement. The proposed transaction is expected to close in July 2011.

Concurrently with the execution of the implementation agreement, Astex entered into support agreements with each Director of SuperGen, pursuant to which each such person agreed to vote his shares of SuperGen common stock. Melanie Toyne Sewell of College Hill (Europe) and Rebecca Skye Dietrich of College Hill (US) acted as public relation advisors to Astex Therapeutics. Michael Ares of Fleishman-Hillard and Alan Roemer of The Trout Group acted as public relation advisors to SuperGen Inc. Marc Recht of Cooley LLP and Kevin Jones of Wragge & Co LLP acted as legal advisors to Astex Therapeutics. Page Mailliard of Wilson Sonsini Goodrich & Rosati acted as a legal advisor to SuperGen Inc.

 

Millennium Pharmaceuticals, Inc. acquired two oncolgy assets from Biogen Idec Inc. (NasdaqGS: BIIB) effective April 5, 2011. The two assets are pan-Raf kinase inhibitor and one additional undisclosed kinase inhibitor program in oncology.

 

Sanofi-Aventis (ENXTPA: SAN) made a bid to acquire Genzyme Corp. (NasdaqGS: GENZ) from SV Life Sciences Advisers LLP, Relational Investors LLC, Carl Icahn and other investors for $17.6 billion in cash on July 29, 2010. Under the terms of the deal, Genzyme shareholders would receive $69 per Genzyme share in cash. BNP Paribas and JP Morgan will provide financing for the deal. The deal is fully financed and is not subject to a financing contingency. Genzyme’s management and employees would play a key role within Sanofi-Aventis following the acquisition.

On August 11, 2010, the Board of Genzyme rejected the offer. At a meeting of financial advisors of Sanofi-Aventis held on August 24, 2010, Genzyme’s Board was still unwilling to have constructive discussions. Sanofi secured financing from BNP Paribas and Société Générale in France, as well as J.P. Morgan Europe in the form of a term loan of upto $15 billion. The transaction is expected to close on December 10, 2010. The deal will be accretive to Sanofi-Aventis.

As of October 4, 2010, Sanofi-Aventis commenced the tender offer and it will expire on December 10, 2010. The transaction has been approved by Sanofi’s Board and subject to regulatory, antitrust and minimum tender condition. The deal is also subject to approval by Board of Genzyme.

On October 7, 2010, Genzyme Board determined that the offer is inadequate and that the offer is not in the best interests of the company. As of October 20, 2010, the deal has been approved by U.S. antitrust regulators. The waiting period under the Hart-Scott Rodino Act has expired. As of December 13, 2010, the offer has been extended till January 21, 2011. Till December 13, 2010, 2.2 million shares have been tendered representing 0.9% of the outstanding shares on a fully-diluted basis. The deal has been approved by the European Commission on January 12, 2011.

The expiration date of the offer is extended to February 15, 2011.

 

Sanofi-Aventis (ENXTPA: SAN) entered into a definitive agreement to acquire Genzyme Corp. (NasdaqGS: GENZ) from SV Life Sciences Advisers LLP, Relational Investors LLC, Carl Icahn and other investors for $21.5 billion in cash on February 16, 2011. Under the terms of the deal, each shareholder will receive $74 and per share in cash. In addition to the cash payment, each Genzyme shareholder will receive one contingent value right for each share they own, entitling the holder to receive additional cash payments if specified milestones related to Lemtrada™ (alemtuzumab MS) are achieved over time or a milestone related to production volumes in 2011 for Cerezyme® and Fabrazyme® is achieved. The transaction is subject to customary closing conditions, listing of shares and registration statement effectiveness. The expiration date of the offer is extended to March 16, 2011. The transaction has been unanimously approved by the Boards of Directors of Sanofi-Aventis and Genzyme. Genzyme Corp will have to pay $575 million in case of termination. The transaction is expected to close early in the second quarter of 2011. The acquisition is expected to be accretive to sanofi-aventis’ business net earnings per share in the first year following closing, and accretive to business net earnings per share.

Board of Directors of Genzyme Corp. unanimously recommended to the shareholders of Genzyme Corp. to tender their shares into the revised tender offer on March 7, 2011. On March 29, 2011, registration statement relating to the contingent value rights offered to Genzyme shareholders is declared effective by the U.S. Securities and Exchange Commission. On April $, 2011, Sanofi-Aventis acquired approximately 84.6% of Genzyme’s outstanding shares of common stock and to allow remaining Genzyme shareholders the opportunity to tender their shares, a subsequent offer period has been extended till April 7, 2011.

Thierry Arachtingi, Nikolaï Eatwell, Evan Cohen, Brian Hoffmann, Cécile Bourdonnas, Dominic Nadeau, Aaron Charney and Daniel Winick of Clifford Chance acted as legal advisors to BNP Paribas, JP Morgan Europe and Société Générale. François Maisonrouge of Evercore Partners and J.P. Morgan acted as financial advisors to Sanofi-Aventis. Kathryn Merryfield, Benjamin Vicentini and Lauren Hanley of Linklaters and Claude Serra, Michael Aiello, Agathe Soilleux, Warren Buhle, Emmanuel Ringeval, Jaclyn Cohen, Campbell Austin, Peter Milligan, Zillah Whittaker, Helene Jaffe, Douglas Nave, Roman Ferla, Greg Danilow, John Neuwirth, Michael Epstein, Jackie Cohen, Megan Pendleton, Andrew Gaines, Eric Schecter, Sarah Dale, Jared Rusman, Stephane Chaouat and Chayim Neubort of Weil, Gotshal & Manges LLP acted as legal advisor to Sanofi-Aventis. Credit Suisse Securities (USA) LLC and The Goldman Sachs Group acted as financial advisors to Genzyme Corp. and Paul M. Kinsella of Ropes & Gray LLP acted as legal advisor to Genzyme Corp. Axel Malkomes of SG Corporate & Investment Banking acted as financial advisor for Sanofi-Aventis. Andrew Brownstein, Greg Ostling and Donald P. Casey of Wachtell Lipton Rosen & Katz acted as legal advisors for Genzyme Corp. Computershare Trust Company, NA acted as depository and MacKenzie Partners acted as information agent to Sanofi-Aventis. Morgan Stanley (NYSE: MS) acted as a financial advisor to Sanofi-Aventis. Innisfree M&A acted as information agent to Genzyme. Kekst and Company Inc. acted as public relations advisor to Genzyme. Casey Cogut, Eric Swedenburg, Jason Breen and Ariel Oxman of Simpson Thacher acted as legal advisors to JPMorgan and Evercore.

 

Sanofi-Aventis (ENXTPA: SAN) completed the acquisition of Genzyme Corp. (NasdaqGS: GENZ) from SV Life Sciences Advisers LLP, Relational Investors LLC, Carl Icahn and other investors on April 8, 2011.

 

Adventrx Pharmaceuticals, Inc. (AMEX: ANX) entered into a definitive agreement to acquire SynthRx, Inc. for $35.5 million in stock on February 12, 2011. Under the terms, Adventrx will issue 1 million shares of Adventrx’s common stock, of which 0.2 million shares shall be deposited in escrow. The escrow amount will be held in escrow for 12 months following the closing of the merger. An additional 1.94 million shares of Adventrx’s common stock will be issued, which subject to vesting shares are subject to various repurchase rights by Adventrx and fully vest, subject to reduction upon certain events, upon achievement of the first milestone. Up to 1 million shares of Adventrx’s common stock will be issued upon achievement of the first milestone. In the event the first milestone is achieved prior to the first anniversary of the closing of the merger, twenty percent (20%) of the first milestone payment shall be deposited in escrow. 3.8 million and 8.6 million shares of Adventrx’s common stock will be issued upon achievement of the second and third milestone respectively.

 

SynthRx stakeholders would be entitled to receive these additional shares of common stock upon successful achievement of development milestones consisting of dosing the first patient in a phase 3 clinical study, acceptance by the U.S. Food and Drug Administration (FDA) of a New Drug Application (NDA) and approval by the FDA of an NDA. If Adventrx’s stockholders do not approve the issuance of the milestone-related shares as required by NYSE Amex listing standards, Adventrx expects to pay SynthRx’s stakeholders in cash the value of the shares it otherwise would have issued, with the NDA acceptance and NDA approval milestone payments payable based on net sales of 188 and all milestone payments payable in quarterly installments. Upon closing, SynthRx would become a wholly-owned subsidiary of Adventrx.

 

The consummation of the merger is subject to certain customary conditions, including, the approval by SynthRx’s stockholders; delivery of audited financial statements of SynthRx for fiscal years 2009 and 2010; obtaining required governmental consents; and Adventrx having obtained a waiver of participation rights under that certain Rights Agreement, dated July 27, 2005. The merger will be terminated if it has not been consummated on or prior to May 2, 2011. Canaccord Genuity Inc. acted as financial advisor for Adventrx Pharmaceuticals. Don Markley of Lippert/Heilshorn & Associates, Inc. acted PR advisor to Adventrx.

 

Adventrx Pharmaceuticals, Inc. (AMEX: ANX) completed the acquisition of SynthRx, Inc. on April 8, 2011. Beal Advisors LLC acted as the financial advisor for Synthrx, Inc.

 

Morphotek, Inc. acquired tumor targeting assets from TransMolecular, Inc. on April 4, 2011. The financial terms of the deal were not disclosed. The consideration included upfront payment and also includes payment on future development milestones. The transaction provides Morphotek and Eisai exclusive ownership of tumor-targeting peptide for therapeutic and diagnostic uses.

 

Morphotek, Inc. completed the acquisition of tumor targeting assets from TransMolecular, Inc. on April 4, 2011.

 


 

News & Events:

 

TopoTarget A/S announced the establishment of the Global Oncology Advisory Board. The members of the board are: Professor Jean-Louis Misset- Professor of Oncology at the University and at the St. Louis Hospital Oncology Division in Paris, France; Dr. Matti Aapro- Dean of the Multidisciplinary Oncology Institute, Genolier, Switzerland; Professor James Cassidy- Professor of Oncology and Head of Academic Unit, University of Glasgow, Scotland; Assistant Professor Alain Catalin Mita- Assistant Professor of Medicine at the University of Texas Health Science Center San Antonio, Texas, US; Professor Hans-Joachim Schmoll- Professor of Internal Medicine and Director of the Department of Haematology and Oncology at the Martin Luther University, Halle-Wittenberg, Germany Dr. Daniel D. Von Hoff- Physician in Chief, Senior Investigator and Director of Clinical Translational Research Division at TGen (Translational Genomics Research Institute) in Phoenix, Arizona, US.

 

Bradmer Pharmaceuticals Inc. announced that its license agreement with Duke University has been terminated. Pursuant to the license agreement, Bradmer licensed certain patent rights relating to a drug, termed Neuradiab(R), for the treatment of glioblastoma multiforme, the most common and advanced form of primary brain cancer. Bradmer’s Phase III clinical trial for Neuradiab was suspended in March 2009 and Bradmer has not pursued any activities relating to the clinical development of Neuradiab since that date. Bradmer is continuing to negotiate with P1 Energy Corp. the terms of a definitive agreement in respect of their previously announced business combination. Completion of the Transaction remains subject to a number of conditions.


 

Strategy & Strategic Alliances:

 

Dainippon Sumitomo Pharma Co. Ltd. and Boston Biomedical, Inc. announced that they have signed a Product Option License Agreement for BBI608 for all oncology indications in Japan and exclusive right of negotiation for BBI608 for the United States and Canada. BBI608 is an orally administered, first-in-class, small molecule anti-cancer drug that targets highly malignant cancer stem cells as well as other heterogeneous cancer cells. In clinical trials to date, BBI608 has shown excellent safety, favorable pharmacokinetics, and encouraging signs of anticancer activity. BBI608 is under phase I extension clinical studies in colorectal cancer and phase Ib/II trials in multiple solid tumor types. Under the terms of the agreement, BBI will receive $15 million of upfront payment and clinical trial support upon signing. Based on the outcome of the clinical trials, DSP has the option to acquire exclusive rights for the development and commercialization for BBI608 in Japan. In addition, DSP has an exclusive negotiation right for the United States and Canada for a certain time. During this option agreement period, DSP will pay a maximum of $55million for part of the development costs of BBI608 and for continuation of the option. Assuming DSP exercise the option for Japan, upon successful clinical development and commercialization of BBI608 in Japan, BBI could receive a maximum of approximately $100million in aggregate, including milestone payments associated with successful development and commercialization, in addition to running royalties. BI608 is a first-in-class, cancer stem cell inhibitor, currently in clinical development. Cancer stem cells (CSCs), being refractory to current cancer therapies, represent an emerging approach for designing the next generation of oncology therapeutics. CSCs are considered to be fundamentally responsible for malignant growth, metastasis, and recurrence. These cells are a subpopulation of cancer cells that have self-renewal ability and can differentiate into the heterogeneous cancer cells that comprise the bulk of the tumor mass. CSCs have been isolated from almost every major type of cancer, and have been found to be intrinsically resistant to current cancer therapies. Targeting CSCs, therefore, holds great promise for fundamentally advancing cancer treatment. BBI608, through its undisclosed molecular target, simultaneously inhibits multiple key cancer cell stemness pathways. BBI608 targets highly malignant CSCs as well as heterogeneous cancer cells. In clinical trials to date, BBI608 has shown excellent safety, favorable pharmacokinetics, and encouraging signs of anticancer activity against a broad range of tumor types. BBI608 is currently in phase I extension in colorectal cancer and phase Ib/II trials for combination therapy with paclitaxel for selected solid tumor types.

 

Roche Holding AG announced that the David H. Koch Institute for Integrative Cancer Research at MIT will be using the Roche LightCycler 480 System, a real-time polymerase chain reaction system for the analysis of gene expression and genetic variation, in advanced cancer research. The Koch Institute plans to use the LightCycler 480 System to support several key areas of research it has identified as being critical for rapid progress toward controlling cancer, such as exploring the molecular and cellular basis of metastasis and engineering the immune system to fight cancer.

 

BioWa, Inc. and Oxford BioTherapeutics Limited announced that they have entered into a license agreement to provide OBT with access to BioWa’s patented POTELLIGENT(R) Technology platform for the development of antibody dependent cellular cytotoxicity (ADCC) enhanced antibodies. OBT intends to use POTELLIGENT(R) Technology to develop, manufacture and commercialize selected ADCC programs from its pipeline of preclinical antibodies for oncology which it has built based upon novel targets identified using its OGAP(R) proteomic database. In return for the license, OBT will pay to BioWa undisclosed license fees, development and commercialization milestones and royalties on sales of any products that it commercializes.

 

Myriad Genetics Inc. signed an agreement with BioMarin Pharmaceutical Inc. to conduct BRCA1 and BRCA2 mutation testing on patients to be enrolled in BioMarin’s Phase I/II clinical study of BMN 673, a novel PARP-inhibitor drug candidate in patients with advanced or recurrent tumors. Under the agreement, Myriad will perform Comprehensive BRACAnalysis(R) with large rearrangement testing to identify the presence of germline mutations in the patients prior to enrolling in the study and provide standard test reports to the clinicians. This is the third agreement between Myriad and pharmaceutical companies developing PARP-inhibitors and is consistent with one of the Company’s goals of becoming a leader in companion diagnostics.

 

ProMetic Life Sciences Inc. announced that it had entered into an agreement with Celgene Corporation for the worldwide rights to a commercial application of ProMetic’s Protein Technologies. Under the terms of this agreement, Abraxis BioScience Inc. will forgive a $10 million long-term debt entered into with ProMetic on February 9, 2010, effectively terminating said loan agreement four years prior to its original term in return for intellectual property rights for specific commercial application of its Protein Technologies within restricted fields of use. This agreement is subject to certain conditions relating to the completion of relevant intellectual property transfer documentation.

 

AlCana Technologies, Inc, University Of British Columbia, and Alnylam Pharmaceuticals, Inc. announced that Alnylam has elected to extend the companies’ RNAi therapeutics research collaboration for a third year. The research collaboration was initiated in August 2009 and focused on the discovery of novel cationic lipids employed in lipid nanoparticles for the systemic delivery of RNAi therapeutics. The research collaboration is funded by Alnylam and the work will be conducted by scientists at UBC and AlCana. Under the terms of the research agreement, Alnylam retains exclusive rights to all new inventions in the RNAi field as well as rights to sublicense any resulting intellectual property to Alnylam’s current and future partners. As part of the original 2009 agreement, Tekmira Pharmaceuticals Corporation receives rights to use any new AlCana/UBC inventions for their own RNAi therapeutic programs licensed under Alnylam intellectual property through its InterfeRx(TM) program.

 

Definiens AG and Cernostics Inc. announced a partnership to develop a multiplexed assay tool for the diagnosis of cancer. Cernostics Inc. will apply Definiens AG’ image analysis technology to develop new molecular diagnostic tests for the treatment of a variety of cancer types. Cernostics Inc. is using Definiens Tissue Studio to develop its cancer diagnostic test, which relies on highly multiplexed panels of fluorescence biomarkers, with the final goal to deploy the solution in the clinical routine. Definiens Tissue Studio enables pathologists to analyze cancers on the cellular and sub-cellular level. Rapid and accurate quantification of cancer characteristics will provide the Cernostics Inc. research team with data on which to build and deploy cancer diagnostic tests. The collaboration with Definiens AG will enable Cernostics Inc. to accelerate development of its pipeline of systems biology-based diagnostic, prognostic and predictive tests.

 

Caliper Life Sciences, Inc. announced that its Caliper Discovery Alliances and Services (CDAS) unit has formed a research collaboration with Catholic Health Initiatives (CHI). The health care system’s Center for Translational Research (CTR), which is part of CHI’s Institute for Research and Innovation, will work with Caliper to develop improved methods for evaluating and predicting the efficacy of new cancer drugs. Under this program, CTR will provide fresh human tumor samples to CDAS for CDAS to perform biomarker and standard-of-care drug resistance/sensitivity studies on these samples. CDAS will grow the CTR samples under various experimental conditions, including traditional two-dimensional cell culture, three-dimensional (3-D) in vitro culture, and in vivo culture in mice, and the CTR will supply key treatment history and diagnostic data for these tumor sources. The drug discovery industry demands better, more clinically relevant drug screening services utilizing cellular models that mimic the function of living tissues to reduce the drug candidate attrition rate between the stages of in vitro and in vivo experimentation. Optimized 3D cell assays or assays performed on human tumor cells maintained in a similar tumor microenvironment under the skin of mice, may provide valuable information to better predict drug efficacy in humans. CDAS provides oncology drug discovery assays based on a variety of biological output parameters such as proliferation, viability, apoptosis or specific biomarkers applied under conventional monolayer cell culture conditions. This new collaboration allows these testing methods to be extended to fresh tumor cells maintained under potentially more natural and disease-relevant conditions.

 

Eisai Co., Ltd. has entered into an option agreement with PRISM BioLab Co., Ltd. Under the terms of the agreement, PRISM shall grant Eisai the option to acquire the exclusive worldwide rights (excluding some countries) to develop and commercialize analogous compounds of the CBP/beta-catenin inhibitor and pharmaceutical products that contain analogous compounds as an active ingredient for the treatment of solid tumors and leukemia, with the right to sublicense. Simultaneously, Eisai has also entered into a license and collaborative research and development agreement with PRISM under which PRISM shall grant Eisai the exclusive worldwide rights (excluding some countries) to develop and commercialize CBP/beta-catenin inhibitor as well as pharmaceutical products that contain CBP/beta-catenin inhibitor as an active ingredient for the treatment of solid tumors and leukemia, with the right to sublicense.

 

Algeta ASA has entered research collaboration with Genzyme Corporation to evaluate the potential of its Thorium platform. Under the terms of the collaboration, Genzyme will provide access to a novel and proprietary tumor-targeting antibody and Algeta will provide access to its Thorium platform to attach the alpha emitting payload thorium-227. Both companies will contribute resources towards the collaboration, which is expected to last for up to a year initially. Thorium-227 is an element (radionuclide) that emits high-energy alpha particles. Such elements are of considerable interest in the treatment of cancer as they are potent at killing tumor cells and have a highly localized effect as a result of the very short range of the alpha particle (2-10 cell diameters). Thorium-227 is linked to tumor-targeting carrier molecules, such as monoclonal antibodies, to reach its target. By conjugating thorium-227 to a number of such molecules, each with a different tumor target, Algeta is exploring the potential to create a pipeline of new-generation alpha-pharmaceuticals to specifically seek and destroy cancers while minimizing damage to surrounding healthy tissues.

Vital Signs #5 – Oncology – April 17th, 2011

By Scott Jordan, Partner — scott@c3f.ca0.myftpupload.com

 

News & Events: Cancer Immunotherapy

One of the most significant milestones in cancer immunotherapy drug development occurred in 2010 with the FDA approval of Dendreon’s Provenge (sipuleucel-T) for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.

However, Provenge’s approval has overshadowed cancer immunotherapy’s marginal success rate. Most immunotherapeutic agents have not shown sufficient activity in early trials, and whereas some were advanced to phase III investigation, most failed in randomized comparisons. With over 333 program failures to date, many cancer vaccines lacked robust evidence of potent immunostimulation as judged by immunological monitoring (~# of new vs. circulating T Cells).

Contributing factors to failures in the clinic may include:

  • Ineffective or marginally effective agents (~quality of Dendritic cells used)
  • Low sensitivity of the detection of immune responses to uncharacterized antigens in the tumor lysates used to pulse Dendritic cells
  • An incomplete understanding of human tumor immunology (cancer cells may not be adequate targets for T cells even when a robust T cell response has been induced by the vaccine)
  • Low MHC expression or other antigen processing and presenting molecule alteration, and insensitivity to the pro-apoptotic signals from T cells would all lead to a disconnect between the results of an immune monitoring assay in peripheral blood and tumor responses
  • Patients not meeting post-surgery inclusion or exclusion criteria
  • Challenge of reliably determining disease response earlier in the data collection process
  • Lack of established surrogate markers, such as immune response making the difficulty of establishing efficacy of an adjuvant immunotherapy

Momentum in the field may be shifting given initiatives planned and facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute, Association for Cancer Immunotherapy (C-IMT) in Europe, and International Society for Biological Therapy of Cancer in the United States supported the redefinition of biological outcome measures and clinical endpoints in cancer immunotherapy.

Recommendations include:

  • Cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes
  • Immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns.
  • Delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials.


Clinical & Regulatory:

Neogenix Oncology, Inc. announced that members of its scientific staff will present laboratory studies of NEO-101, a novel monoclonal antibody in development to diagnose and treat pancreatic and colorectal cancers. The presentation is scheduled at the American Association of Cancer Research (AACR) 102(nd) Annual Meeting being held April 1-6, 2011 at the Orange County Convention Center, Orlando, FL, USA. NEO-101 (NPC-1C, or Ensituximab) is a chimeric monoclonal antibody being developed as a novel biological treatment for pancreatic and colorectal cancer and is currently in Phase I clinical trials at The Johns Hopkins University Hospital, Duke University Medical Center and North Shore University/Long Island Jewish Medical Center. NEO-101 is the first in the Neogenix pipeline of antibodies intended to target specific cancers. The NEO-101 target appears to be a variant of MUC5AC that is expressed specifically by human colon and pancreatic tumor tissues and cell lines that in testing to date, have only occasionally shown, minimal and weak cross-reactivity to certain normal GI tract tissues. The preclinical data to be presented includes in vitro mechanism of action, immuno fluorescent cell staining, in vivo anti-tumor efficacy, bio-distribution, and toxicokinetic studies.

 

Alnylam Pharmaceuticals, Inc. announced that it has completed enrollment in its ALN-VSP Phase I multi-center, multinational, open label, dose escalation clinical trial. The study’s objectives were to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced solid tumors with liver involvement. ALN-VSP was administered to over 40 patients at doses ranging from 0.1 to 1.5 mg/kg, with multiple patients continuing to receive therapy on the study.

 

Radient Pharmaceuticals Corporation announced preliminary results from its clinical study conducted in collaboration with a well-recognized, large third-party not-for-profit group practice and its affiliates for the validation of RPC’s US FDA’s cleared Onko’s Sure(r) in vitro diagnostic (IVD) cancer test. The purpose of the study was to determine the effectiveness of Onko-Sure(r) (DR-70) as a useful tool in the detection of colorectal cancer in all stages of colorectal cancer (CRC), especially early stages where effective diagnosis leads to better patient prognosis. In addition, this study focused on the effectiveness of Onko-Sure(r), Carcinoembryonic Antigen (CEA) and the combination of these two tumor markers for additional clinical value. Based on preliminary results, RPC’s Onko-Sure(r) IVD cancer test shows a statistical advantage over CEA in detecting CRC in the early stages of colorectal cancer. Furthermore, when Onko-Sure(r) was combined with CEA, the sensitivity of the combined test was substantially improved as opposed to using CEA alone. RPC plans to disseminate these results in a peer-reviewed journal, either independently or with other third party healthcare organizations. Additionally, RPC plans to present these results to physicians at international oncology conferences and scientific meetings.

 

Amgen Inc., Millennium Pharmaceuticals, Inc. and Takeda Pharmaceutical Co. Ltd. announced top-line results from the MONET1 pivotal Phase 3 trial evaluating motesanib administered in combination with paclitaxel and carboplatin in 1,090 patients with advanced non-squamous non-small cell lung cancer. The trial did not meet its primary objective of demonstrating an improvement in overall survival (OS) (hazard ratio 0.90, 95% CI 0.78 — 1.04, p=0.14). Overall, the adverse event profile for motesanib was consistent with that seen in previous motesanib studies in NSCLC. Notable adverse events reported included hypertension, GI events (abdominal pain, diarrhea, nausea, and vomiting), gallbladder events (cholecystitis, gallbladder enlargement), fatigue, and hematological events (neutropenia, thrombocytopenia). Serious adverse events were more frequently reported in the motesanib arm. MONET1 (MOtesanib NSCLC Efficacy and Tolerability Study) is a Phase 3, multicenter, randomized, placebo-controlled, double-blind trial that enrolled more than 1,000 men and women with NSCLC. Patients were randomized to receive either paclitaxel (200 mg/m2 IV Q3W), carboplatin (target AUC of 6 mg/mL x min IV Q3W), and motesanib (125 mg PO QD) or paclitaxel, carboplatin, and placebo. The primary endpoint of the study was OS, and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), association of placental growth factor with OS, duration of response, and safety and tolerability. Motesanib is an investigational, orally-administered small molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptors, and stem cell factor receptor.

 

Roche Holding AG announced that the second of two Phase III trials evaluating Lucentis (ranibizumab injection) in patients with diabetic macular edema (DME) met its primary endpoint. The primary endpoint of the study, known as RIDE, showed that after 24 months a significantly greater number of patients who received Lucentis, compared to those who received placebo (sham) injections, were able to read at least 15 additional letters on an eye chart than they could at the start of the study. The safety results were consistent with previous Lucentis Phase III trials and no new significant safety findings were observed. Further analyses of the data are ongoing. Topline results from the RIDE study will be presented at the EURETINA Congress in London on May 29, 2011. DME is an eye condition characterized by swelling of the retina, which can occur in patients with type 1 or type 2 diabetes and can cause blurred vision, severe vision loss and blindness.1 DME is a leading cause of blindness among the working-age population in most developed countries, 2 and there are currently no U.S. Food & Drug Administration (FDA) approved medications to treat DME. At 24 months, 33.6% of patients (42/125) who received 0.3 mg Lucentis and 45.7% of patients (58/127) who received 0.5 mg Lucentis were able to read at least 15 more letters on the eye chart than they were at baseline, compared to 12.3% of patients (16/130) who received sham injections. The difference between each Lucentis dose group and the sham injection group was statistically significant. The study was not designed to compare the Lucentis doses with each other.

 


 

Corporate Finance:

 

Genta Incorporated reported unaudited consolidated earnings results for the fourth quarter and year ended December 31, 2010. For the fourth quarter of 2010, the company reported a net loss of $33.9 million, or net loss per basic and diluted share of $14.46 per share, compared with a net loss of $11.7 million or $317.71 per basic and diluted share, for the fourth quarter of 2009. Net product sales were $0.065 against $0.038 for the same period a year ago. Loss before income tax benefit was $34.363 million against $14.594 million for the same period a year ago.

For the year ended December 31, 2010, the company reported a net loss of $167.3 million, or $246.04 per basic and diluted share, compared with a net loss of $86.3 million, or $4,200.99 per basic and diluted share, for the year ended December 31, 2009. Net cash used in operating activities for the twelve months ended December 31, 2010 was $14.3 million or approximately $1.2 million per month. Net product sales were $0.257 million against $0.218 for the same period a year ago. Loss before income tax benefit was $167.796 million against $86.301 million for the same period a year ago.

 

The company projects that average net monthly cash outflow will be approximately $1.5 million during 2011.

 

Nippon Kayaku Co. Ltd. reported consolidated earnings results for the nine months ended February 28, 2011. For the period, the company reported increasing net profit 2.7% to JPY 7.4 billion. Revenue was up 6.9% to JPY 111 billion. Operating profit increased 35.7% to JPY 15.9 billion and ordinary profit rose 29% to JPY 15 billion. Earnings per share rose from JPY 39.8 to JPY 40.9 per share.

 

The company provided earnings guidance for the year ending May 31, 2011. The company maintained net profit forecast of JPY 11.5 billion and full-year revenue forecast is unchanged at JPY 151 billion.

 

AVI Biopharma, Inc. has filed a Follow-on Equity Offering.

 

Helix Biopharma Corp. (TSX: HBP) announced a private placement of 1,652,719 units at a price of $2.39 per unit for gross proceeds of $3,949,999 on March 28, 2011. Each unit consists of one common share and one common share purchase warrant. Each warrant entitles the holder to purchase one common share of the company at a price of $3.35 for up to five years after the closing date of the private placement. Net proceeds after expenses are $3,900,000. Jack Kay, a Director of the company and his wife acquired 209,205 units and a related party, Kay Family Charitable Foundation of which Kay is a trustee acquired an additional 209,205 units. As a result, Kay’s holdings in the company including his wife and the Foundation is 1.32% of the common shares currently outstanding and if warrants to purchase up to 418,410 common shares and stock options to purchase up to 205,000 common shares are exercised, then the stake will increase to 2.24% in the company.

 

Advanced Life Sciences Holdings, Inc., 1 : 30, Stock Split or Significant Stock Dividend, Mar-29-2011

 


 

Legal & Litigation:

 

The U.S. Court of Appeals for the Federal Circuit will hear arguments on April 4, 2011 in a landmark case centering on whether human genes should be patentable. The court battle started in 2009, when the Assn. for Molecular Pathology and others sued Myriad Genetics Inc. challenging the validity of Myriad’s patents on two genes linked to breast and ovarian cancer. Myriad’s sole rights to the genes and its diagnostic analysis leaves women unable to confirm their test results elsewhere, and other women cannot afford Myriad’s $3,000 test.


 

Mergers & Acquisitions:

 

Rumors are going around that Torrent Pharmaceuticals Ltd. may sell stake to AstraZeneca PLC. A sourceclose to the matter said, “Torrent and AstraZeneca are in talks to work jointly in the area of clinical trials, co-marketing and developing new molecules.” The news report mentioned that as part of the deal, which is likely to be struck sometime in 2011, AstraZeneca will outsource molecules of its patented drugs to be sold in developed countries. According to the sources, most of these would be in the chronic therapeutic segments such as cardio, diabetology, oncology and psychiatry. They added that a deal is likely to add INR 5 billion to Torrent Pharma’s top line. According to the report, the company has denied any stake sale. Spokesperson for Torrent stated, “The ongoing market rumors about a possible stake sale by Torrent Pharmaceuticals to AstraZeneca are absolutely baseless and untrue and the management denies the same. There is no move on the part of the promoters of Torrent Pharma or its management to sell any stake in the company to any players, national or global.”

 

Cephalon Inc (Nasdaq: CEPH) made an offer to acquire remaining 72.48% stake in ChemGenex Pharmaceuticals Limited (ASX: CXS) from Merck Sante, GBS Venture Partners Ltd and other shareholders for approximately AUD 140 million in cash on March 29, 2011. Cephalon will make an offer of AUD 0.7 for each ChemGenex Pharmaceuticals share, cum dividends and other rights and an offer of AUD 0.02 for each ASX-listed ChemGenex option. Cephalon intends to fund the transaction consideration from its available cash on hand. Cephalon Inc holds a prebid stake of 27.52% in ChemGenex.The offer for shares is subject to Cephalon CXS having a relevant interest in at least 90% of ChemGenex shares, no material adverse change, during the condition period, no member of the ChemGenex group should conduct its business otherwise than in the ordinary course, no change of control event should be triggered, no approval issued by a regulatory authority to or otherwise held by any member of the ChemGenex group is or is able to be revoked, withdrawn, terminated or varied, approval of US Hart-Scott-Rodino Antitrust Improvements Act, no prescribed occurrences.

 

The deal is also subject to no member of the ChemGenex Group acquiring any one or more entities, businesses or assets the price, or aggregate price, of which exceeds AUD 1 million, disposing any one or more entities, businesses or assets the price, or aggregate price, of which exceeds AUD1 million, entering into any agreement involving a commitment greater than AUD 1 million or the term of which cannot be terminated within 6 months, incurring any indebtedness or issues any debt securities, entering into any joint venture, shareholders, partnership or strategic alliance agreement, certain other conditions and the option offer having become or having been declared free of all conditions. The offer for ChemGenex listed options is subject to the same conditions which are for the offer for shares except that before and at the end of the offer period, Cephalon CXS should have a relevant interest in at least 90% of ChemGenex options and the share offer having become or having been declared free of all conditions. Subject to obtaining advice on the applicable U.S. law requirements, Cephalon will consider extending the share offer to holders of ChemGenex American Depository Receipts (ADRs) if compliance with those requirements is not unduly onerous or impracticable.

 

The Directors of ChemGenex Pharmaceuticals have recommended the transaction in the absence of a superior offer. David Petrie and Michael Gregory of Merrill Lynch acted as the financial advisor and Johnson Winter & Slattery acted as the legal advisor to Cephalon. Canaccord Genuity acted as the financial advisor and McCullough Robertson acted as the legal advisor to ChemGenex. Rebecca Wilson of Buchan Consulting acted as the public relations advisor to ChemGenex.


 

News & Events:

 

Source Precision Medicine, Inc. announced that 16 molecular diagnostic development programs will be offered for sale on April 29, 2011. These molecular diagnostic programs are blood-based, not tissue-based. Eight programs cover the following cancers: prostate, lung, breast, cervical, ovarian, colon, bladder and melanoma. In addition, two programs cover infectious diseases: sepsis and hepatitis C infection; three programs cover autoimmune diseases: rheumatoid arthritis, multiple sclerosis, lupus, osteoarthritis and ocular and one covers transplant rejection.


 

Strategy & Strategic Alliances:

 

Ono Pharma has signed an exclusive licensing agreement with OncoTherapy Science Inc. to develop, manufacture and commercialise the latter’s therapeutic peptide vaccine, the Japanese pharma announced yesterday. Under the terms of agreement, the indication for the therapeutic vaccine covers all types of cancers including hepatocellular carcinoma in the geographical areas of Japan, South Korea, and Taiwan. Ono Pharma will also hold an option to widen territory based on development status. In return, it will make an upfront payment, development and commercial milestone payments and sales royalties to the biotech. No financial figure has been disclosed.

 

Calypso Medical Technologies, Inc. announced the installation of a Calypso System at The Harley Street Clinic. With its GPS for the Body technology, the Calypso System use miniature implanted Beacon transponders to provide precise, continuous information on the location of the tumor during external beam radiation therapy.

 

Alnylam Pharmaceuticals, Inc. announced that it has earned a $10 million technology transfer payment from Takeda Pharmaceutical Company Limited as part of the strategic alliance the companies formed in May 2008. This payment is related to the achievement of certain pre-defined objectives in the transfer of Alnylam’s platform technology, including documents, materials, and know-how, to Takeda for the development of RNAi therapeutics. Alnylam had previously received $140 million in upfront and technology transfer payments from Takeda. Alnylam is also eligible to receive significant milestones and royalties related to the Takeda’s successful advancement of RNAi therapeutic products, and has retained certain product opt-in rights in the U.S. market. The Alnylam-Takeda alliance, which is valued at potentially over $1 billion, represents the industry’s broadest RNAi therapeutics partnership. The agreement provides Takeda with broad, worldwide, non-exclusive access to and enablement with Alnylam’s RNAi therapeutics platform technology and intellectual property in the fields of oncology and metabolic disease, with the right to expand the number of therapeutic fields in the future. In addition, it includes a collaboration and cross-license of delivery technologies between the two companies, and a drug discovery collaboration on certain RNAi targets. Alnylam also has the right to opt-in and co-develop and co-commercialize Takeda RNAi therapeutic programs in the U.S. market on a 50-50 basis; the opt-in right can be exercised up until the start of Phase III clinical trials.

 

Pacific Edge Limited and Healthscope Ltd. have signed an agreement to market Pacific Edge’s (PE) novel diagnostic test for the detection of bladder cancer, Cxbladder® across the Tasman. Under the terms of the agreement, Healthscope Pathology will market and offer laboratory services to urologists and general practitioners (GP) for the detection of bladder cancer using Cxbladder® in Australia. Pacific Edge will provide services to New Zealand urologists and GPs through its subsidiary Pacific Edge Diagnostics NZ Ltd, with its diagnostic laboratory based in Dunedin. Pacific Edge will retain the rights to the rest of the world for the marketing of Cxbladder®. The terms of the license agreement are confidential.

 

Champions Biotechnology, Inc. has signed an agreement with Cephalon Inc., under which Champions will conduct low passage Tumorgraft(TM) studies on two proprietary chemical compounds, CEP-32496, an inhibitor of mutant B-Raf, and CEP-37440, a selective dual ALK-FAK inhibitor, provided by Cephalon to determine the activity or response in potential clinical indications. The results of these studies will be used to inform the future clinical development path of these compounds. Under the terms of the agreement, Cephalon will pay Champions an initiation fee of $1.39 million by April 15, 2011, and will also pay Champions various amounts totaling $27 million upon achieving certain milestones. In addition, Cephalon will pay Champions royalties on any commercialized products developed under the agreement.

 

Biomoda Inc. announced the signing of a Memorandum of Understanding with the University of Texas Health Science Center at San Antonio to collaborate on research to optimize the CyPath(R) diagnostic assay for lung cancer.

 

Morphotek, Inc. entered into a collaboration and license agreement with Biocare Medical, LLC. Under the agreement, the parties will collaborate to develop and commercialize an immunohistochemical (IHC) diagnostic kit utilizing Morphotek’s proprietary monoclonal antibody to specifically detect human folate receptor alpha (FRA) with Biocare’s intelliPATH Automated Stainer. The agreement provides Biocare with a non-exclusive license to develop, manufacture and commercialize an IHC kit for detection of FRA on formalin-fixed paraffin-embedded (FFPE) tumor tissues. FRA is a cell surface protein that is over-expressed in a variety of cancers including non-small cell lung adenocarcinoma and ovarian carcinoma. Studies have found its expression variable among different cancer types. In light of this variability, a diagnostic assay that can identify patients with FRA-positive cancers may enable better diagnosis and treatment of patients affected with FRA-expressing cancers. FRA is the target of Morphotek’s therapeutic candidate, farletuzumab, which is currently being tested in several clinical trials against different types of cancers.

 

deCODE Biostructures, Inc. and ChemDiv, Inc. have announced the formation of a strategic drug discovery and development alliance which will provide biotech and pharmaceutical companies with fully integrated structure based small molecule discovery services, from gene to clinic. This collaboration enhances both companies’ portfolios of offerings to their customers and creates synergistic effects by delivering high quality services and best value to the industry. Partnership with ChemDiv will provide an access to broad bioscreening and assay development platforms, CMC, formulation and API capabilities, pharmacology and translational research focused on oncology, CNS, CV/metabolics, inflammation and anti-infective and rare disease therapeutic areas. The collaboration announced establishes a strategic preferred partner co-marketing relationship which allows ChemDiv’s clients to access Emerald’s structural biology expertise in solving challenging protein targets. Emerald’s clients can now benefit from the range of ChemDiv’s discovery and development services. The companies will utilize their distinctive translational and fully integrated drug discovery and development platform to support collaborative efforts.

 

Ariad Pharmaceuticals Inc. and MolecularMD Corp. announced an exclusive collaboration agreement in which MolecularMD will develop and commercialize a companion diagnostic test to identify the T315I mutation of the BCR-ABL gene in patients with chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia. ARIAD is advancing its investigational, pan-BCR-ABL inhibitor, ponatinib, in the pivotal PACE trial of patients with resistant or intolerant CML and Ph+ ALL, or those with the T315I mutation. MolecularMD has performed BCR-ABL mutation testing with its standardized and validated sequencing test in patients enrolled in ARIAD’s earlier Phase 1 trial of ponatinib and now is conducting similar testing prior to patient treatment in the PACE trial. As part of this collaboration agreement, MolecularMD will further optimize its currently available sequencing test and will file a Premarket Approval Application with the U.S. Food and Drug Administration to support commercialization of the diagnostic test. The companies expect MolecularMD to submit the PMA at approximately the same time as ARIAD files its New Drug Application for ponatinib in 2012. MolecularMD will also seek a CE Mark for a companion diagnostic test kit in Europe. Once approved, MolecularMD will have responsibility for commercializing the T315I diagnostic test. Under terms of the collaboration agreement, ARIAD will reimburse MolecularMD for predefined expenses for the development of the T315I diagnostic test. ARIAD will also pay MolecularMD milestones for achievement of key development and regulatory activities. The MolecularMD companion diagnostic test is being developed to identify CML and Ph+ ALL patients who have the T315I mutation. A companion diagnostic test is not necessary to support the broader potential use of ponatinib in patients who are resistant or intolerant to the current second-generation BCR-ABL inhibitors, as being studied in the PACE trial. Many mutations in addition to T315I account for resistance to currently marketed BCR-ABL inhibitors.

Vital Signs #4 – Oncology – April 3, 2011

By Scott Jordan, Partner — scott@c3f.ca0.myftpupload.com

 

Clinical & Regulatory:

Neogenix Oncology, Inc. announced that members of its scientific staff will present laboratory studies of NEO-101, a novel monoclonal antibody in development to diagnose and treat pancreatic and colorectal cancers. The presentation is scheduled at the American Association of Cancer Research (AACR) 102(nd) Annual Meeting being held April 1-6, 2011 at the Orange County Convention Center, Orlando, FL, USA. NEO-101 (NPC-1C, or Ensituximab) is a chimeric monoclonal antibody being developed as a novel biological treatment for pancreatic and colorectal cancer and is currently in Phase I clinical trials at The Johns Hopkins University Hospital, Duke University Medical Center and North Shore University/Long Island Jewish Medical Center. NEO-101 is the first in the Neogenix pipeline of antibodies intended to target specific cancers. The NEO-101 target appears to be a variant of MUC5AC that is expressed specifically by human colon and pancreatic tumor tissues and cell lines that in testing to date, have only occasionally shown, minimal and weak cross-reactivity to certain normal GI tract tissues. The preclinical data to be presented includes in vitro mechanism of action, immuno fluorescent cell staining, in vivo anti-tumor efficacy, bio-distribution, and toxicokinetic studies.

Alnylam Pharmaceuticals, Inc. announced that it has completed enrollment in its ALN-VSP Phase I multi-center, multinational, open label, dose escalation clinical trial. The study’s objectives were to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced solid tumors with liver involvement. ALN-VSP was administered to over 40 patients at doses ranging from 0.1 to 1.5 mg/kg, with multiple patients continuing to receive therapy on the study.

Radient Pharmaceuticals Corporation announced preliminary results from its clinical study conducted in collaboration with a well-recognized, large third-party not-for-profit group practice and its affiliates for the validation of RPC’s US FDA’s cleared Onko’s Sure(r) in vitro diagnostic (IVD) cancer test. The purpose of the study was to determine the effectiveness of Onko-Sure(r) (DR-70) as a useful tool in the detection of colorectal cancer in all stages of colorectal cancer (CRC), especially early stages where effective diagnosis leads to better patient prognosis. In addition, this study focused on the effectiveness of Onko-Sure(r), Carcinoembryonic Antigen (CEA) and the combination of these two tumor markers for additional clinical value. Based on preliminary results, RPC’s Onko-Sure(r) IVD cancer test shows a statistical advantage over CEA in detecting CRC in the early stages of colorectal cancer. Furthermore, when Onko-Sure(r) was combined with CEA, the sensitivity of the combined test was substantially improved as opposed to using CEA alone. RPC plans to disseminate these results in a peer-reviewed journal, either independently or with other third party healthcare organizations. Additionally, RPC plans to present these results to physicians at international oncology conferences and scientific meetings.

Amgen Inc., Millennium Pharmaceuticals, Inc. and Takeda Pharmaceutical Co. Ltd. announced top-line results from the MONET1 pivotal Phase 3 trial evaluating motesanib administered in combination with paclitaxel and carboplatin in 1,090 patients with advanced non-squamous non-small cell lung cancer. The trial did not meet its primary objective of demonstrating an improvement in overall survival (OS) (hazard ratio 0.90, 95% CI 0.78 — 1.04, p=0.14). Overall, the adverse event profile for motesanib was consistent with that seen in previous motesanib studies in NSCLC. Notable adverse events reported included hypertension, GI events (abdominal pain, diarrhea, nausea, and vomiting), gallbladder events (cholecystitis, gallbladder enlargement), fatigue, and hematological events (neutropenia, thrombocytopenia). Serious adverse events were more frequently reported in the motesanib arm. MONET1 (MOtesanib NSCLC Efficacy and Tolerability Study) is a Phase 3, multicenter, randomized, placebo-controlled, double-blind trial that enrolled more than 1,000 men and women with NSCLC. Patients were randomized to receive either paclitaxel (200 mg/m2 IV Q3W), carboplatin (target AUC of 6 mg/mL x min IV Q3W), and motesanib (125 mg PO QD) or paclitaxel, carboplatin, and placebo. The primary endpoint of the study was OS, and secondary endpoints included progression-free survival (PFS), objective response rate (ORR), association of placental growth factor with OS, duration of response, and safety and tolerability. Motesanib is an investigational, orally-administered small molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptors, and stem cell factor receptor.

Roche Holding AG announced that the second of two Phase III trials evaluating Lucentis (ranibizumab injection) in patients with diabetic macular edema (DME) met its primary endpoint. The primary endpoint of the study, known as RIDE, showed that after 24 months a significantly greater number of patients who received Lucentis, compared to those who received placebo (sham) injections, were able to read at least 15 additional letters on an eye chart than they could at the start of the study. The safety results were consistent with previous Lucentis Phase III trials and no new significant safety findings were observed. Further analyses of the data are ongoing. Topline results from the RIDE study will be presented at the EURETINA Congress in London on May 29, 2011. DME is an eye condition characterized by swelling of the retina, which can occur in patients with type 1 or type 2 diabetes and can cause blurred vision, severe vision loss and blindness.1 DME is a leading cause of blindness among the working-age population in most developed countries, 2 and there are currently no U.S. Food & Drug Administration (FDA) approved medications to treat DME. At 24 months, 33.6% of patients (42/125) who received 0.3 mg Lucentis and 45.7% of patients (58/127) who received 0.5 mg Lucentis were able to read at least 15 more letters on the eye chart than they were at baseline, compared to 12.3% of patients (16/130) who received sham injections. The difference between each Lucentis dose group and the sham injection group was statistically significant. The study was not designed to compare the Lucentis doses with each other.


Corporate Finance:

Genta Incorporated reported unaudited consolidated earnings results for the fourth quarter and year ended December 31, 2010. For the fourth quarter of 2010, the company reported a net loss of $33.9 million, or net loss per basic and diluted share of $14.46 per share, compared with a net loss of $11.7 million or $317.71 per basic and diluted share, for the fourth quarter of 2009. Net product sales were $0.065 against $0.038 for the same period a year ago. Loss before income tax benefit was $34.363 million against $14.594 million for the same period a year ago.

For the year ended December 31, 2010, the company reported a net loss of $167.3 million, or $246.04 per basic and diluted share, compared with a net loss of $86.3 million, or $4,200.99 per basic and diluted share, for the year ended December 31, 2009. Net cash used in operating activities for the twelve months ended December 31, 2010 was $14.3 million or approximately $1.2 million per month. Net product sales were $0.257 million against $0.218 for the same period a year ago. Loss before income tax benefit was $167.796 million against $86.301 million for the same period a year ago.

The company projects that average net monthly cash outflow will be approximately $1.5 million during 2011.

 

Nippon Kayaku Co. Ltd. reported consolidated earnings results for the nine months ended February 28, 2011. For the period, the company reported increasing net profit 2.7% to JPY 7.4 billion. Revenue was up 6.9% to JPY 111 billion. Operating profit increased 35.7% to JPY 15.9 billion and ordinary profit rose 29% to JPY 15 billion. Earnings per share rose from JPY 39.8 to JPY 40.9 per share.

The company provided earnings guidance for the year ending May 31, 2011. The company maintained net profit forecast of JPY 11.5 billion and full-year revenue forecast is unchanged at JPY 151 billion.

 

AVI Biopharma, Inc. has filed a Follow-on Equity Offering.

 

Helix Biopharma Corp. (TSX: HBP) announced a private placement of 1,652,719 units at a price of $2.39 per unit for gross proceeds of $3,949,999 on March 28, 2011. Each unit consists of one common share and one common share purchase warrant. Each warrant entitles the holder to purchase one common share of the company at a price of $3.35 for up to five years after the closing date of the private placement. Net proceeds after expenses are $3,900,000. Jack Kay, a Director of the company and his wife acquired 209,205 units and a related party, Kay Family Charitable Foundation of which Kay is a trustee acquired an additional 209,205 units. As a result, Kay’s holdings in the company including his wife and the Foundation is 1.32% of the common shares currently outstanding and if warrants to purchase up to 418,410 common shares and stock options to purchase up to 205,000 common shares are exercised, then the stake will increase to 2.24% in the company.

 

Advanced Life Sciences Holdings, Inc., 1 : 30, Stock Split or Significant Stock Dividend, Mar-29-2011

 


Legal & Litigation:

The U.S. Court of Appeals for the Federal Circuit will hear arguments on April 4, 2011 in a landmark case centering on whether human genes should be patentable. The court battle started in 2009, when the Assn. for Molecular Pathology and others sued Myriad Genetics Inc. challenging the validity of Myriad’s patents on two genes linked to breast and ovarian cancer. Myriad’s sole rights to the genes and its diagnostic analysis leaves women unable to confirm their test results elsewhere, and other women cannot afford Myriad’s $3,000 test.


Mergers & Acquisitions:

Rumors are going around that Torrent Pharmaceuticals Ltd. may sell stake to AstraZeneca PLC. A sourceclose to the matter said, “Torrent and AstraZeneca are in talks to work jointly in the area of clinical trials, co-marketing and developing new molecules.” The news report mentioned that as part of the deal, which is likely to be struck sometime in 2011, AstraZeneca will outsource molecules of its patented drugs to be sold in developed countries. According to the sources, most of these would be in the chronic therapeutic segments such as cardio, diabetology, oncology and psychiatry. They added that a deal is likely to add INR 5 billion to Torrent Pharma’s top line. According to the report, the company has denied any stake sale. Spokesperson for Torrent stated, “The ongoing market rumors about a possible stake sale by Torrent Pharmaceuticals to AstraZeneca are absolutely baseless and untrue and the management denies the same. There is no move on the part of the promoters of Torrent Pharma or its management to sell any stake in the company to any players, national or global.”

 

Cephalon Inc (Nasdaq: CEPH) made an offer to acquire remaining 72.48% stake in ChemGenex Pharmaceuticals Limited (ASX: CXS) from Merck Sante, GBS Venture Partners Ltd and other shareholders for approximately AUD 140 million in cash on March 29, 2011. Cephalon will make an offer of AUD 0.7 for each ChemGenex Pharmaceuticals share, cum dividends and other rights and an offer of AUD 0.02 for each ASX-listed ChemGenex option. Cephalon intends to fund the transaction consideration from its available cash on hand. Cephalon Inc holds a prebid stake of 27.52% in ChemGenex.The offer for shares is subject to Cephalon CXS having a relevant interest in at least 90% of ChemGenex shares, no material adverse change, during the condition period, no member of the ChemGenex group should conduct its business otherwise than in the ordinary course, no change of control event should be triggered, no approval issued by a regulatory authority to or otherwise held by any member of the ChemGenex group is or is able to be revoked, withdrawn, terminated or varied, approval of US Hart-Scott-Rodino Antitrust Improvements Act, no prescribed occurrences.

The deal is also subject to no member of the ChemGenex Group acquiring any one or more entities, businesses or assets the price, or aggregate price, of which exceeds AUD 1 million, disposing any one or more entities, businesses or assets the price, or aggregate price, of which exceeds AUD1 million, entering into any agreement involving a commitment greater than AUD 1 million or the term of which cannot be terminated within 6 months, incurring any indebtedness or issues any debt securities, entering into any joint venture, shareholders, partnership or strategic alliance agreement, certain other conditions and the option offer having become or having been declared free of all conditions. The offer for ChemGenex listed options is subject to the same conditions which are for the offer for shares except that before and at the end of the offer period, Cephalon CXS should have a relevant interest in at least 90% of ChemGenex options and the share offer having become or having been declared free of all conditions. Subject to obtaining advice on the applicable U.S. law requirements, Cephalon will consider extending the share offer to holders of ChemGenex American Depository Receipts (ADRs) if compliance with those requirements is not unduly onerous or impracticable.

The Directors of ChemGenex Pharmaceuticals have recommended the transaction in the absence of a superior offer. David Petrie and Michael Gregory of Merrill Lynch acted as the financial advisor and Johnson Winter & Slattery acted as the legal advisor to Cephalon. Canaccord Genuity acted as the financial advisor and McCullough Robertson acted as the legal advisor to ChemGenex. Rebecca Wilson of Buchan Consulting acted as the public relations advisor to ChemGenex.


News & Events:

Source Precision Medicine, Inc. announced that 16 molecular diagnostic development programs will be offered for sale on April 29, 2011. These molecular diagnostic programs are blood-based, not tissue-based. Eight programs cover the following cancers: prostate, lung, breast, cervical, ovarian, colon, bladder and melanoma. In addition, two programs cover infectious diseases: sepsis and hepatitis C infection; three programs cover autoimmune diseases: rheumatoid arthritis, multiple sclerosis, lupus, osteoarthritis and ocular and one covers transplant rejection.


Strategy & Strategic Alliances:

Ono Pharma has signed an exclusive licensing agreement with OncoTherapy Science Inc. to develop, manufacture and commercialise the latter’s therapeutic peptide vaccine, the Japanese pharma announced yesterday. Under the terms of agreement, the indication for the therapeutic vaccine covers all types of cancers including hepatocellular carcinoma in the geographical areas of Japan, South Korea, and Taiwan. Ono Pharma will also hold an option to widen territory based on development status. In return, it will make an upfront payment, development and commercial milestone payments and sales royalties to the biotech. No financial figure has been disclosed.

 

Calypso Medical Technologies, Inc. announced the installation of a Calypso System at The Harley Street Clinic. With its GPS for the Body technology, the Calypso System use miniature implanted Beacon transponders to provide precise, continuous information on the location of the tumor during external beam radiation therapy.

 

Alnylam Pharmaceuticals, Inc. announced that it has earned a $10 million technology transfer payment from Takeda Pharmaceutical Company Limited as part of the strategic alliance the companies formed in May 2008. This payment is related to the achievement of certain pre-defined objectives in the transfer of Alnylam’s platform technology, including documents, materials, and know-how, to Takeda for the development of RNAi therapeutics. Alnylam had previously received $140 million in upfront and technology transfer payments from Takeda. Alnylam is also eligible to receive significant milestones and royalties related to the Takeda’s successful advancement of RNAi therapeutic products, and has retained certain product opt-in rights in the U.S. market. The Alnylam-Takeda alliance, which is valued at potentially over $1 billion, represents the industry’s broadest RNAi therapeutics partnership. The agreement provides Takeda with broad, worldwide, non-exclusive access to and enablement with Alnylam’s RNAi therapeutics platform technology and intellectual property in the fields of oncology and metabolic disease, with the right to expand the number of therapeutic fields in the future. In addition, it includes a collaboration and cross-license of delivery technologies between the two companies, and a drug discovery collaboration on certain RNAi targets. Alnylam also has the right to opt-in and co-develop and co-commercialize Takeda RNAi therapeutic programs in the U.S. market on a 50-50 basis; the opt-in right can be exercised up until the start of Phase III clinical trials.

 

Pacific Edge Limited and Healthscope Ltd. have signed an agreement to market Pacific Edge’s (PE) novel diagnostic test for the detection of bladder cancer, Cxbladder® across the Tasman. Under the terms of the agreement, Healthscope Pathology will market and offer laboratory services to urologists and general practitioners (GP) for the detection of bladder cancer using Cxbladder® in Australia. Pacific Edge will provide services to New Zealand urologists and GPs through its subsidiary Pacific Edge Diagnostics NZ Ltd, with its diagnostic laboratory based in Dunedin. Pacific Edge will retain the rights to the rest of the world for the marketing of Cxbladder®. The terms of the license agreement are confidential.

 

Champions Biotechnology, Inc. has signed an agreement with Cephalon Inc., under which Champions will conduct low passage Tumorgraft(TM) studies on two proprietary chemical compounds, CEP-32496, an inhibitor of mutant B-Raf, and CEP-37440, a selective dual ALK-FAK inhibitor, provided by Cephalon to determine the activity or response in potential clinical indications. The results of these studies will be used to inform the future clinical development path of these compounds. Under the terms of the agreement, Cephalon will pay Champions an initiation fee of $1.39 million by April 15, 2011, and will also pay Champions various amounts totaling $27 million upon achieving certain milestones. In addition, Cephalon will pay Champions royalties on any commercialized products developed under the agreement.

 

Biomoda Inc. announced the signing of a Memorandum of Understanding with the University of Texas Health Science Center at San Antonio to collaborate on research to optimize the CyPath(R) diagnostic assay for lung cancer.

 

Morphotek, Inc. entered into a collaboration and license agreement with Biocare Medical, LLC.Under the agreement, the parties will collaborate to develop and commercialize an immunohistochemical (IHC) diagnostic kit utilizing Morphotek’s proprietary monoclonal antibody to specifically detect human folate receptor alpha (FRA) with Biocare’s intelliPATH Automated Stainer. The agreement provides Biocare with a non-exclusive license to develop, manufacture and commercialize an IHC kit for detection of FRA on formalin-fixed paraffin-embedded (FFPE) tumor tissues. FRA is a cell surface protein that is over-expressed in a variety of cancers including non-small cell lung adenocarcinoma and ovarian carcinoma. Studies have found its expression variable among different cancer types. In light of this variability, a diagnostic assay that can identify patients with FRA-positive cancers may enable better diagnosis and treatment of patients affected with FRA-expressing cancers. FRA is the target of Morphotek’s therapeutic candidate, farletuzumab, which is currently being tested in several clinical trials against different types of cancers.

 

deCODE Biostructures, Inc. and ChemDiv, Inc. have announced the formation of a strategic drug discovery and development alliance which will provide biotech and pharmaceutical companies with fully integrated structure based small molecule discovery services, from gene to clinic. This collaboration enhances both companies’ portfolios of offerings to their customers and creates synergistic effects by delivering high quality services and best value to the industry. Partnership with ChemDiv will provide an access to broad bioscreening and assay development platforms, CMC, formulation and API capabilities, pharmacology and translational research focused on oncology, CNS, CV/metabolics, inflammation and anti-infective and rare disease therapeutic areas. The collaboration announced establishes a strategic preferred partner co-marketing relationship which allows ChemDiv’s clients to access Emerald’s structural biology expertise in solving challenging protein targets. Emerald’s clients can now benefit from the range of ChemDiv’s discovery and development services. The companies will utilize their distinctive translational and fully integrated drug discovery and development platform to support collaborative efforts.

 

Ariad Pharmaceuticals Inc. and MolecularMD Corp. announced an exclusive collaboration agreement in which MolecularMD will develop and commercialize a companion diagnostic test to identify the T315I mutation of the BCR-ABL gene in patients with chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia. ARIAD is advancing its investigational, pan-BCR-ABL inhibitor, ponatinib, in the pivotal PACE trial of patients with resistant or intolerant CML and Ph+ ALL, or those with the T315I mutation. MolecularMD has performed BCR-ABL mutation testing with its standardized and validated sequencing test in patients enrolled in ARIAD’s earlier Phase 1 trial of ponatinib and now is conducting similar testing prior to patient treatment in the PACE trial. As part of this collaboration agreement, MolecularMD will further optimize its currently available sequencing test and will file a Premarket Approval Application with the U.S. Food and Drug Administration to support commercialization of the diagnostic test. The companies expect MolecularMD to submit the PMA at approximately the same time as ARIAD files its New Drug Application for ponatinib in 2012. MolecularMD will also seek a CE Mark for a companion diagnostic test kit in Europe. Once approved, MolecularMD will have responsibility for commercializing the T315I diagnostic test. Under terms of the collaboration agreement, ARIAD will reimburse MolecularMD for predefined expenses for the development of the T315I diagnostic test. ARIAD will also pay MolecularMD milestones for achievement of key development and regulatory activities. The MolecularMD companion diagnostic test is being developed to identify CML and Ph+ ALL patients who have the T315I mutation. A companion diagnostic test is not necessary to support the broader potential use of ponatinib in patients who are resistant or intolerant to the current second-generation BCR-ABL inhibitors, as being studied in the PACE trial. Many mutations in addition to T315I account for resistance to currently marketed BCR-ABL inhibitors.

Vital Signs #3 – Oncology – April 3, 2011

By Scott Jordan, Partner — scott@c3f.ca0.myftpupload.com

  1. News & Events: Next Generation Sequencing
  2. News Summary

News & Events: Next Generation Sequencing 

Increasingly Big Pharma/Biotech are relying on biomarkers, molecular segmentation, and targeted agents to enhance clinical development/de-risk drug development efforts as evidenced by the following news releases:

Daiichi Sankyo’s acquisition of Plexxikon

Daiichi Sankyo announced it will pay $805 million upfront and up to $130 million in near-term milestones for Plexxikon, an oncology developer with promising clinical data in melanoma. In August of 2010, researchers announced that nearly all melanoma patients enrolled in a clinical trial of PLX4032 responded to treatment (PLX4032 is an oral drug that targets the oncogene BRAF mutation present in half of melanoma cancers and about eight percent of all solid tumors). Interim data from a Phase 3 controlled study of PLX4032 in previously untreated metastatic melanoma patients with the BRAF mutation met both co-primary endpoints. Patients treated with PLX4032 had improved overall survival (OS) and improved progression-free survival (PFS) compared to patients treated with decarbazine, the current standard of care. 81 percent of patients had tumor shrinkage of at least 30 percent.

Roche/Curis – Hedgehog Pathway

Roche Holding AG reported positive results from a Phase 2 study of investigational Hedgehog Pathway Inhibitor vismodegib (RG3616/GDC-0449) for the treatment of advanced basal cell carcinoma (aBCC). According to the results, the compound met its primary endpoint of overall response rate in terms of shrinking tumors in study participants. Safety data were also positive, as shown in earlier studies.

Hedgehog, a key regulator of cell growth and differentiation during development, controls epithelial and mesenchymal interactions in many tissues during embryogenesis. Mutations cause constitutive hedgehog pathway signaling, which in basal-cell carcinomas can mediate unrestrained proliferation of basal cells of the skin. For this reason, blocking the hedgehog pathway may be useful in treating patients with basal-cell carcinoma.

 

Next Generation Sequencing

The days of drug development wherein researchers go after a relatively vaguely defined form of cancer based on its organ of origin, give it to all patients in a clinical trial with the related form of cancer, and hope that 25-30 percent will respond to therapy is coming to an end. Drug development is in a revolutionary state of change where patients who are most likely to respond to a given treatment based on their molecular signatures are rationally selected for inclusion in clinical trials. By sequencing tumor cell vs. normal cell DNA and isolating the variations/SNPs amongst other information/data, investigators give the “right drug to the right patient” statistically increasing response rates and delivering on the promise of “personalized” medicine.

These developments have not escaped Big Pharma/Biotech who are willing to pay enormous premiums to acquire/license personalized medical treatments like Plexxikon’s PLX4032.  Other ongoing personalized studies include those for Triple Negative Breast Cancer (TGen) and Pfizer’s c-Met and ALK inhibitor (5% of NSCLC patients have ALK mutations); both designed to target a clearly defined genetic population of cancer patients.

One of the most promising areas of personalized drug development capitalizing is the area of Epigenetics. Epigenetics refers to the regulation of genes with mechanisms other than changes to the underlying DNA sequence and such processes are widely believed to play a central role in the development and progression of almost all cancers (drive tumor progression). Such Epigenetic processes are controlled by DNA methylation and histone modifications.

A leader in Epigenics is a biotechnology company, Epizyme, whose vision is to enroll patients with a certain pathological form of cancer and take blood or biopsy samples that will enable researchers to divide patients into separate groups, one for those who have an overeactive form of the given epigenetic enzyme, the other for those who don’t. By looking at how Epigenetic profiles of patients differ, Epizyme hopes to generate a higher percentage of responders which should be highly predictive of what happens when the drug enters much larger clinical trials (help to drive better prognostic decisions).

One of the largest impediments to reaching the full potential of personalized medicine is the lack of payer reimbursement for sequencing patient genomes. In select cases, foundations have stepped-up to fill the gap left from the lack of public/private reimbursement.

Clinical & Regulatory:

Mersana Therapeutics, Inc. announced the initiation of a Phase 1b extension study with its lead cancer product, XMT-1001, a novel DNA topoisomerase I inhibitor based on the company’s Fleximer(R) polymer conjugate platform, in second-line gastric cancer and second-/third-line non-small cell lung cancer. The study will be carried out in 10 clinical centers in the US. The Phase 1b follows the successful completion of a 74-patient Phase 1 clinical trial, which demonstrated high and prolonged plasma levels of XMT-1001 active release products and a safety profile free of the toxicities normally associated with topoisomerase 1 inhibitors, such as hemorrhagic cystitis and diarrhea. Additionally, XMT-1001 showed promising evidence of clinical activity, including tumor shrinkage and prolonged stable disease, in a heavily pre-treated patient population.

Oncolytics Biotech Inc. announced that it has completed patient enrollment in its U.S. Phase 2 clinical trial (REO 015) using intravenous administration of REOLYSIN in combination with paclitaxel and carboplatin in patients with advanced head and neck cancers. This trial was a 14-patient, single arm, open-label, dose-targeted, non-randomized trial of REOLYSIN given intravenously in combination with a standard dosage of paclitaxel and carboplatin. This study was performed in part to confirm the results of UK Phase II study, which enrolled a slightly different patient population, and to support ongoing Phase III study in platinum resistant head and neck cancers.

Manhattan Scientifics, Inc. announced that The Gray Sheet has written about an initial clinical trial that has enrolled its first 35 patients to measure leukemia cells using a nanotechnology-based magnetic imaging method developed by Senior Scientific, which has licensed the technology to Manhattan Scientifics, Inc. A first-in-man clinical trial to measure very small levels of residual leukemia cells using a unique nanotechnology-based magnetic imaging method has enrolled its first 35 patients. The technology, in development by Senior Scientific and nanomedicine-focused investment firm Manhattan Scientifics, is still years from reaching the market, but the firms say they are in active partnering discussions with several large drug, device and imaging companies. The trial, which will enroll 60 patients in all, is expected to be completed within two years. In leukemia, the focus is on monitoring the effect of chemotherapy by detecting residual disease. The technique also has applications in gauging therapy response in a range of other cancers.

To discuss the progress made within each of Access‘ programs, including an update on commercial launch activities and schedule for MuGard, the company’s oral mucositis supportive care product, its Cobalamin CobOral and CobaCyte programs, as well as the advancement of both its Thiarabine Phase 1/2a trial in hematological malignancies at M.D. Anderson Cancer Center, and ProLindac phase 2 combination trial in recurrent ovarian cancer.

Roche Holding AG has reported positive results from a Phase II study of investigational Hedgehog Pathway Inhibitor vismodegib (RG3616/GDC-0449) for the treatment of advanced basal cell carcinoma (aBCC), a severe and debilitating form of skin cancer. According to the results, the compound met its primary endpoint of overall response rate in terms of shrinking tumours in study participants. Safety data were also positive, as shown in earlier studies. Roche has said full results of the study will be presented at an upcoming scientific meeting.

Bristol-Myers Squibb Company announced that a clinical trial, known as study 024 – of its investigational compound ipilimumab has met the primary endpoint of improving overall survival in previously-untreated patients with metastatic melanoma. Study 024 was designed to assess overall survival in unresectable stage III or stage IV melanoma patients who have not received prior therapy. The study compares ipilimumab 10mg/kg in combination with chemotherapy vs. chemotherapy alone. An abstract of the 024 data will be submitted to the American Society of Clinical Oncology for potential presentation at the Annual Meeting in June of this year. A regulatory filing for ipilimumab, based on a study known as 020, is currently under review by the U.S. Food and Drug Administration and other health authorities worldwide. The filings are based on study 020, which assessed overall survival in previously-treated unresectable stage III or stage IV melanoma patients. Study 020 compared ipilimumab 3 mg/kg + gp100 vaccine vs. gp100 vaccine alone and ipilimumab along vs. gp100 vaccine alone. The PDUFA date for the U.S. filing is March 26, 2011.

Cell Therapeutics, Inc. announced that it has initiated its randomized pivotal trial of pixantrone for the treatment of relapsed/refractory diffuse large B-cell lymphoma (“DLBCL”). The clinical trial is now open to patient enrollment. The trial, referred to as the PIX-R or PIX 306 trial, will compare a combination of pixantrone plus rituximab to a combination of gemcitabine plus rituximab in patients with relapsed or refractory DLBCL who have received one to three prior lines of therapy. The PIX-R trial utilizes progression free survival (“PFS”) and overall survival as co-primary endpoints of the study. The PIX-R trial is targeting to enroll approximately 350 patients over 18 months and will include patients who have failed at least one line of previous therapy and patients who are not candidates for myeloablative chemotherapy and stem cell transplant. The PIX-R trial may serve as either a post-marketing commitment trial or as a follow-on pivotal trial depending on the outcome of a formal appeal that CTI submitted to the Food & Drug Administration’s Office of New Drugs in the FDA’s Center for Drug Evaluation and Research in December 2010 regarding its 2010 decision about CTI’s new drug application (the “NDA”) for pixantrone. The NDA for pixantrone was based on the results of the PIX 301 trial, a randomized trial comparing pixantrone as monotherapy to a choice of standard single-agent chemotherapy in relapsed/refractory aggressive non-Hodgkin’s lymphoma (“NHL”) patients. CTI expects a decision regarding its appeal in the second quarter of 2011. The PIX-R trial is designed to be a randomized, multicenter study comparing pixantrone plus rituximab to gemcitabine plus rituximab in patients with relapsed or refractory DLBCL or DLBCL transformed from follicular lymphoma who have received one to three prior lines of therapy, including CHOP-R or an equivalent regimen. The patients to be enrolled in the PIX-R trial cannot be eligible for high-dose (myeloablative) chemotherapy and stem cell transplant, but patients who relapse after such a procedure are eligible. The co-primary endpoints for the PIX-R trial are PFS and OS with secondary endpoints including overall response rate (“ORR”) (ORR equals complete responses plus partial responses), complete response rate and safety. CTI is targeting to enroll 350 patients over 18 months in the PIX-R trial.

Curis Inc. announced a positive outcome from a pivotal phase II clinical trial conducted by Roche and Genentech, Curis’ collaborator and a wholly owned member of the Roche Group, of GDC-0449, a first-in-class hedgehog pathway inhibitor, in patients with advanced basal cell carcinoma (BCC). Genentech informed Curis that the study met its primary endpoint of achieving a target overall response rate, showing that GDC-0449 shrank advanced BCC tumors in a pre-defined percentage of people in the study. A preliminary safety assessment showed the most common adverse events were consistent with previous experience with vismodegib. A detailed safety assessment is ongoing. Roche has indicated that it anticipates making at least one regulatory submission in 2011 to seek approval to commercialize GDC-0449. Genentech plans to submit the data from the clinical trial for presentation at a future medical meeting. Roche also informed Curis that GDC-0449 (also known as RG3616) now has a generic name approved by the World Health Organization, vismodegib (pronounced vis-mo-DE-jib). ERIVANCE BCC is an international, single-arm, multi-center, two-cohort, open-label phase II study that enrolled 104 patients with advanced BCC, including metastatic and/or locally advanced BCC, defined as patients whose lesions are not appropriate for surgery, or for whom surgery would result in substantial deformity. Study participants received 150 mg vismodegib once daily until disease progression. The primary endpoint of the study was overall response rate (tumor shrinkage) as assessed by independent reviewers. Secondary endpoints of the study included overall response rate as assessed by study investigators, duration of response, progression-free survival, overall survival and the safety profile. A preliminary safety assessment showed the most common adverse events were muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite and diarrhea. Serious adverse events were observed, including fatal events. The deaths are being further evaluated, but do not appear to be related to vismodegib. Genentech is also evaluating vismodegib in a phase II trial in people with operable forms of BCC, which opened in October 2010. Additionally, vismodegib is being evaluated by third-party investigators in a number of other cancers and in people with BCC who have Gorlin syndrome.

Sanofi-Aventis announced it has received marketing authorization from the European Commission for JEVTANA® (cabazitaxel) in combination with prednisone/prednisolone for the treatment of patients with metastatic hormone-refractory prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. JEVTANA is the first approved agent to significantly extend overall survival in mHRPC patients whose disease has progressed during or after treatment containing docetaxel (15.1 months median overall survival vs 12.7 months in the mitoxantrone arm; HR=0.70 (95% CI: 0.59-0.83); P<0.0001). The approval from the European Commission followed a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The decision is based on the results from the Phase III TROPIC clinical study involving 755 patients with mHRPC previously treated with a docetaxel-containing treatment regimen. The European Commission decision is applicable to the 27 Member States of the European Union (EU) as well as Iceland, Lichtenstein and Norway. JEVTANA was previously approved in the US, Israel, Curaçao and Brazil.


Corporate Finance:

Antisoma PLC has announced that it has ended its offer period, as it has no takeover bid under consideration at the moment, nor does it expect one. The company had announced on February 8 that it plans to seek a deal to boost shareholders value, said today that its board was looking for the best ways to invest cash resources to benefit shareholders. It added that it was still reviewing options to exploit its basic intellectual property, but will no longer invest in biopharmaceutical programs.

Advanced Life Sciences Holdings, Inc. reported consolidated earnings results for the fourth quarter and full year ended December 31, 2010. For the quarter, the company reported loss from operations of $3,298,208 compared to $1,165,975 for the same period last year. Net loss attributable to Advanced Life Sciences Holdings, Inc. was $3,305,881, or $0.01 per basic and diluted share compared to $1,452,954, or $0.02 per basic and diluted share for the same period last year. The increase in the net loss for the quarter is primarily due to a non-cash impairment charge which was partially offset by reduced salary and benefit costs and other operating expenses associated with the development of the company’s lead antibiotic, Restanza. Cash used in operating activities during the quarter was approximately $1.0 million.

For the year, the company reported loss from operations of $8,628,642 compared to $7,991,939 for the same period last year. Net loss attributable to Advanced Life Sciences Holdings, Inc. was $9,321,994, or $0.06 per basic and diluted share on total revenue of $752,853 compared to $9,163,232, or $0.16 per basic and diluted share on total revenue of $2,793,191 for the same period last year. Cash used in operating activities for the full year was approximately $6.4 million.


Mergers & Acquisitions:

Tesaro, Inc. sigened a license agreement to acquire Anaplastic Lymphoma Kinase program of Amgen Inc. (NasdaqGS: AMGN) on March 22, 2011.


News & Events:

Takeda Pharmaceutical Co. Ltd. established a wholly owned holding company named Takeda (China) Holdings Ltd. in Shanghai on March 21, 2011 that will oversee Takeda’s overall business in China. This new company will be responsible for the feasibility study of the strategies for future business expansion in China and its implementation, and will have functions such as administration, and development, control cash/investment management including those necessary for the increase of the sales force mentioned above, acceleration of development of new products, and improving and renovating the manufacturing facilities of Tianjin Takeda.


Strategy & Strategic Alliances:

Sanofi-Aventis announced a research collaboration with Columbia University Medical Center for the development of innovative diabetes medicines. This three-year research collaboration, with the laboratory of Dr. Gerard Karsenty, will investigate the role of the osteoblast-secreted peptide, osteocalcin, in diabetes management.

Cancer Genetics, Inc. (CGI) and Aptiv Solutions have formed a strategic partnership focused on delivering comprehensive solutions to biopharmaceutical and medical device firms conducting clinical trials for oncology therapeutics. Together, CGI and Aptiv Solutions will provide biopharmaceutical firms with a better understanding of modes of action of a variety of therapeutics and the role for biomarkers in the oncology drug development process. Early insight in complex diseases and complicated patients garnered by using genomic technologies and other methodologies will drive informed decisions and successful development of targeted therapies, personalized medicine and other new therapeutics. The collaboration will provide customers with the products and services necessary to bring oncology therapeutics to their patients faster and at a reduced cost.

Seattle Genetics Inc. has entered into a collaboration agreement with Abbott under which Abbott will pay an upfront fee of $8 million for rights to utilize Seattle Genetics’ antibody-drug conjugate, or ADC, technology with antibodies to a single oncology target. Abbott is responsible for research, product development, manufacturing and commercialization of any ADC products under the collaboration. Pending achievement of certain development, regulatory and commercial milestones, Seattle Genetics is eligible to receive from Abbott up to approximately $200 million in milestone payments, as well as royalties on worldwide net sales of any resulting ADC products. Seattle Genetics also will receive annual maintenance fees and research support payments for assistance provided to Abbott under the collaboration. Seattle Genetics has 11 active ADC collaborations. There are currently 11 ADCs in clinical development across both internal and collaborator pipelines using Seattle Genetics’ technology.

Eli Lilly and Co. announced that it will continue its venture capital investment in China’s biopharmaceutical industry. The move will to strengthen its research and development (R&D) strength and expand its presence in China.

Ariad Pharmaceuticals Inc. announced that it has elected to exercise its option with Merck & Co. Inc. to co-promote ridaforolimus, an investigational mTOR inhibitor in the sarcoma indication upon its potential approval in the United States in 2012. Based on the terms of the license agreement that Ariad and Merck entered into in May 2010 for the development, manufacture and commercialization of ridaforolimus in oncology, Ariad has the option to co-promote ridaforolimus with up to 20% of the sales effort for the product in all indications in the U.S., and Merck will compensate Ariad for its sales efforts.

Tesaro Inc. announced the signing of an agreement with Amgen Inc. granting TESARO exclusive worldwide rights for the development, manufacture, commercialization and distribution of small molecule inhibitors of Anaplastic Lymphoma Kinase (ALK). TESARO plans to develop one or more compounds for oncology indications, including the treatment of patients with non-small cell lung cancer (NSCLC) whose tumors are ALK-positive. The agreement includes an upfront payment and potential future payments and royalties associated with the achievement of certain development and commercial milestones. Abnormal ALK fusion proteins are thought to be a key driver of certain types of cancers, including a sub-population of NSCLC as demonstrated in recent clinical trials of an ALK inhibitor. Sub-populations of other cancers including lymphoma and neuroblastoma are also associated with abnormal expression of ALK proteins. ALK is generally not expressed in normal adult tissue and therefore represents a promising molecular target for the development of a cancer therapeutic. Amgen’s oral, small molecule ALK inhibitors are highly potent and selective, and possess desirable pharmaceutical properties.

Dako Denmark A/S and the Epitomics, Inc., announced that they have entered into a collaboration which will allow the companies to unite competencies to provide the Anatomic Pathology market with state-of-the-art antibodies. Dako’s expertise within the field of human cancer diagnostics, including development of new diagnostic antibodies relevant in identifying, differentiating and characterizing tumors, and Epitomics’ exclusive intellectual property rights and expertise within development and production of rabbit monoclonal antibodies are the key ingredients to future development of routine diagnostics, prognostics and predictive immunohistochemical assays, also known as companion diagnostics or PharmacoDiagnostics (PharmDxTM). Besides the development and launch of new state-of-the-art monoclonal antibodies the strategic alliance between Dako and Epitomics also includes a technology transfer from Epitomic’s to Dako’s facilities.

Vital Signs #2 – Oncology – March 14, 2011

By Scott Jordan, Partner — scott@c3f.ca0.myftpupload.com

  1. News & Events: Avastin – Anti-Angiogenic or Vascular Permeability Factor
  2. News Summary

News & Events: Avastin – Anti-Angiogenic or Vascular Permeability Factor

 

The theory that Avastin kills tumors by cutting of blood supply is open to question because there is little evidence it works on its own.  Prior to being classified as an anti-angiogenesis agent (tumor growth can be stopped by turning off a cancer cell’s access to blood by deactivating a chemical known as vascular endothelial growth factor or VEGF, which spurs blood-vessel growth) Avastin was referred to as a Vascular Permeability Factor (VPF) agent.

Recent studies have added credence to the VPF mechanism of action (MoA) argument.  Adding Avastin to a weak chemotherapy backbone results in pronounced efficacy versus when added to a strong chemotherapy backbone like modern combination regimens wherein the added benefit of Avastin is modest.  Follow-up studies of Avastin in colorectal cancer with newer types of chemotherapy, Folfox and Xelox, increased progression free survival for just 1.4 months and offered no significant improvement in survival (versus registration approval study using older chemotherapy regimen – added five months of survival).   Tests with two types of chemotherapy against lung cancer resulted in an outcome similar to that of later performed colorectal cancer studies.  When combined with slightly more powerful Cisplatin chemotherapy (widely prescribed in Europe), Avastin did not improve overall survival and had a smaller effect on progression-free survival.

Building upon the validity of the Vascular Permeability Factor theory in cancer therapy, recent studies including JNCI’s “Stromal Depletion Goes on Trial in Pancreatic Cancer” (Vol. 102, Issue 7, April 7, 2010) and Cancer Cell’s “Pancreatic Cancer – Could It Be that Simple? A Different Context of Vulnerability” postulate stroma blocks drug penetration contributing to cancer survival.  Several combination therapies are now in clinical trials to test the “stromal depletion hypothesis” including Abraxane (nab-paclitaxel) in pancreatic cancer (30% of those diagnosed with pancreatic cancer have stroma-rich hypovascular tumors that cannot be resected because the tumor encases the superior mesenteric artery).

Tumor stromal inflammatory cells (lymphocytes, macrophages, mast cells) and stromal fibroblasts oftentimes comprise up to 50-70% of tumor mass. Tumor cells co-evolve with stromal cells and there is active biodirectional communication between stromal and tumor cells. Ability of tumor-associated stromal cells to induce EMT (Epithelial-mesenchymal transition or transformation – program of development of biological cells characterized by loss of cell adhesion, repression of E-cadherin expression, and increased cell mobility)  in tumor cells has been well established. Additional evidence strongly suggests that tumor-associated stromal cells provide paracrine stimuli for mesenchymal cell growth and survival. Primary epithelial tumor cells can undergo EMT and become mesenchymal in order to metastasize and in the process lose sensitivity to many drugs that target epithelial tumors; drug and drug combinations that target EMT form the basis of rational selection of therapies to enhance EGFR responsiveness.

Abraxis (company that developed and markets Abraxane/nab-paclitaxel) reported in the Journal National Cancer Institute (2004; 96:90-1) that albumin in nab-paclitaxel actively binds to the protein SPARC in pancreatic tumors further concentrating the drug in the tumor. The effect leads to a “stromal collapse. ”  The SPARC protein is highly concentrated in the stroma and positive SPARC expression predicts poor clinical outcome.

In response, leading clinical oncologist, Dr. Daniel Von Hoff, launched a Phase I/II trial of nab-paclitaxel in combination with gemcitabine in metastatic pancreatic cancer.  Results presented at the 2009 American Society of Clinical Oncology (ASCO) meeting detailed of 58 evaluable patients treated with Stage IV (metastatic) disease, 23 achieved a partial response, and 22 stable disease. Median time to progression-free survival was 6.9 months and overall survival was 10.3 months.  For the 44 patients treated at the best dose of nab-paclitaxel, the median progression-free survival was 7.9 months, and the median survival had not been reached.  By comparison, median survival for patients treated with gemcitabine alone is 5.9 months, and combining it with erlotinib (Tarceva) gives only 2 more weeks.  A Phase III trial launched in March 2009 in metastatic pancreatic cancer enrolling 630 patients with a primary endpoint of survival.

The debate over Avastin’s mechanism of action (MoA) will be debated for some time given the failure of Avastin in combination with modern chemotherapy regimens (pointing toward a hypothesis that in weaker chemotherapy regimens, Avastin depletes the stromal layer and allows more chemotherapy to reach the tumor) and recent positive outcomes in treating cancer with stromal depletion agents.

In the next issue of “Vital Signs” we will explore the role of EMT/CTGF (Connective Tissue Growth Factor) in the maintenance of cancer stem cells (CSCs) and explore promising emerging growth companies with therapeutic programs targeting CSCs.

 


Clinical & Regulatory:

 

Helix BioPharma Corp. announced that it has filed a clinical trial application with the Central Register of Clinical Trials at the Polish Ministry of Health seeking approval to perform its planned Phase I/II clinical safety, tolerability and preliminary efficacy study of its lung cancer drug candidate L-DOS47. L-DOS47 is Helix’s first therapeutic immunoconjugate drug candidate under development based upon the Company’s novel DOS47 technology, which is designed to modify the microenvironmental conditions of cancer cells in a manner that leads to their destruction. L-DOS47 is intended to offer an innovative approach to the first-line treatment of inoperable, locally advanced, recurrent or metastatic, non-small cell lung cancer. The CTA review process in Poland typically requires 60 days, during which the reviewers will decide if an applicant is permitted to proceed with its proposed clinical trial. Additional information may be requested from the applicant, which could extend the review period. About the Planned Phase I/II Study: The proposed Phase I/II study is planned to be an open-label, non-randomized study to evaluate the safety, tolerability and preliminary efficacy of L-DOS47 alone and in combination with chemotherapy or radiation therapy. The study is planned to be conducted in patients with inoperable, locally advanced, recurrent or metastatic non-squamous NSCLC, using a multi-arm design whereby patients will be recruited into one of four treatment arms: (1) L-DOS47 monotherapy; (2) L-DOS47 + vinorelbine; (3) L-DOS47 + vinorelbine + cisplatin; or (4) L-DOS47 + radiation therapy. Vinorelbine, cisplatin and radiation therapy are all common treatments used for NSCLC.

 

Oncolytics Biotech Inc. announced that enrollment has been completed in a U.K. translational clinical trial investigating intravenous administration of REOLYSIN in patients with metastatic colorectal cancer prior to surgical resection of liver metastases (REO 013). The principal investigator is Professor Alan Melcher of St. James’s University Hospital and the trial is sponsored by the University of Leeds, UK. The trial was an open-label, non-randomized, single centre study of REOLYSIN given intravenously to patients for five consecutive days in advance of their scheduled operations to remove colorectal cancer deposits metastatic to the liver. After surgery, the tumour and surrounding liver tissue were assessed for viral status and anti-tumour effects. The primary objectives of the trial are to assess the presence, replication and anti-cancer effects of reovirus within liver metastases after intravenous administration of REOLYSIN by examination of the resected tumour. Secondary objectives include assessing the anti-tumour activity and safety profile of REOLYSIN, and monitoring the humoral and cellular immune response to REOLYSIN. Eligible patients included those with histologically proven colorectal cancer, planned for potentially curative surgical resection of liver metastases. A total of 10 patients were treated in the study. The results are expected to be fully reported in 2011.

 

Amgen Inc. announced the publication of results from a pivotal Phase 3 study of 1,776 advanced cancer patients with different types of solid tumors (not including breast and prostate cancer) or multiple myeloma, which compared XGEVA(TM) (denosumab) to Zometa(R) (zoledronic acid) in preventing skeletal-related events (SREs). The study, which appeared in the Journal of Clinical Oncology, found that XGEVA was non-inferior to Zometa in delaying or preventing SREs. XGEVA, the first and only RANK Ligand inhibitor indicated for the prevention of SREs in patients with bone metastases from solid tumors was approved by the U.S. Food and Drug Administration (FDA) on Nov. 18, 2010. The approval was based in part on results described in this publication. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma. For the primary endpoint of this study, the median time to first on-study SRE (defined as fracture, radiation to bone, surgery to bone, or spinal cord compression) was 20.6 months for patients receiving XGEVA and 16.3 months for patients receiving Zometa (hazard ratio 0.84, 95% CI: 0.71-0.98), which is statistically significant for non-inferiority (p=0.0007). Although numerically greater, the delay in the time to first SRE associated with XGEVA was not statistically superior compared to Zometa based upon the statistical testing strategy (adjusted p=0.06) (secondary endpoint). The time to first- and subsequent SRE was also numerically greater but not statistically superior compared to Zometa (hazard ratio 0.90, 95% CI: 0.77-1.04, p=0.14) (secondary endpoint). In a subgroup analysis of patients with multiple myeloma, mortality appeared to be higher for denosumab-treated patients compared to those in the control arm (hazard ratio [95% CI] of 2.26 [1.13, 4.50]; n = 180). The limited number of patients in this subgroup, however, precludes definitive conclusions regarding the effects of XGEVA in multiple myeloma patients.

 

Fate Therapeutics, Inc. reported preliminary data from an ongoing Phase 1b clinical trial of FT1050 at the 2011 BMT Tandem Meetings in Honolulu, Hawaii. The goal of the Phase 1b trial, which is being conducted at the Dana-Farber Cancer Institute and Massachusetts General Hospital, is to determine the safety and tolerability of introducing FT1050 during the standard course of dual umbilical cord blood transplant in adult patients with hematologic malignancies, such as leukemia and lymphoma, who have undergone nonmyeloablative conditioning therapy. Fate Therapeutics is developing FT1050 to improve the overall efficiency of hematopoietic stem cell (HSC) support by enhancing HSC homing to and proliferation in the bone marrow. In the ongoing Phase 1b clinical trial, after a reduced-intensity conditioning regimen, each patient receives two umbilical cord blood units for hematopoietic reconstitution: one treated ex vivo at the point-of-care with FT1050 and one untreated. Fifteen subjects of an anticipated 21 have been enrolled to date, with the last six having received an umbilical cord blood unit using the current FT1050 treatment protocol designed to enhance activity; the first nine patients received an umbilical cord blood unit using an earlier version of the FT1050 treatment protocol designed to assess safety. The investigators evaluated the safety of FT1050 as well as the time to initial hematopoietic reconstitution, and which cord blood unit ultimately contributed most to blood count recovery. The average time to engraftment for the six patients who were treated under the current protocol was 18.5 days compared to a historic average of approximately 21 days. In addition, five of these six patients engrafted with the FT1050 treated cord blood unit, suggesting that FT1050 may confer preferential engraftment. In all 15 patients, the safety profile did not appear to differ from that of a standard double umbilical cord transplant. To date, only one patient has experienced Grade 2 or higher acute graft versus host disease. Ten of 15 patients remain alive and disease-free. Accrual is ongoing. In addition, Fate Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to FT1050 for the ex vivo treatment of human allogeneic hematopoietic stem cells to enhance stem cell engraftment by treating neutropenia, thrombocytopenia, lymphopenia and anemia. The Company has also received a positive recommendation by the Committee for Orphan Medicinal Products for orphan designation in the European Union.

 

AB Science S.A. announced publication in The Veterinary Journal of results from a preclinical study showing that masitinib has potential as a chemosensitizer. This study, conducted by Dr. Douglas Thamm (VMD, Diplomate ACVIM Oncology; Colorado State University) and colleagues, investigated the ability of masitinib to sensitize different canine cancer cell lines to various chemotherapeutic agents. Results showed that masitinib sensitized numerous tumor cell lines from different origins (breast, bladder, melanoma, lymphoma, etc.) to chemotherapeutic drugs such as doxorubicin, gemcitabine and vinblastine. These data also provide additional weight to findings from studies showing that masitinib can enhance the antiproliferative effects of gemcitabine in human pancreatic cancer, including gemcitabine-resistant cell lines, which is a property not seen with other tyrosine kinase inhibitors (Humbert et al. PLoS One, 2010). Masitinib was the first ever approved anticancer drug in veterinary medicine, receiving approval from the European Medicines Agency (EMA) under the trade name Masivet. Masitinib has also recently become obtainable in the United States under the trade name Kinavet CA-1, having received conditional approval in December 2010 from the US Food and Drug Administration (FDA) for treatment of recurrent or nonresectable Grade II and Grade II cutaneous mast cell tumors in dogs that have not previously received radiotherapy and/or chemotherapy except corticosteroids. AB Science is developing masitinib in veterinary medicine in oncology, including several studies to further investigate masitinib’s potential as a chemosensitizer, as well as in non-oncology diseases, such as canine atopic dermatitis or asthma in cats. A summary of masitinib’s veterinary clinical development program is provided below (note that this list of indications reflects the development program of masitinib in veterinary medicine and should not be interpreted as a list of indications for which masitinib has demonstrated efficacy). Besides using the animal health segment as a source of revenues to finance its clinical development program in human medicine, AB Science is also using veterinary medicine as a platform to discover new indications for its lead compound masitinib and translate this use into human medicine.

 

ImmuPharma Plc announced encouraging results from its ongoing phase I/IIa clinical trial in cancer patients: around half of the cancer patients that have undergone treatment with ImmuPharma’s drug candidate IPP-204106 are in stable condition (their disease has stopped progressing) without any other drug treatment. All the patients that enrolled in the study were suffering from advanced cancer with metastases and had all failed their previous treatments with other existing cancer drugs. The third dose level of IPP-204106 has just begun in the next group of patients. ImmuPharma’s clinical trial began last summer and up to now two lower dose levels have been tested. The initial dose level of 1 mg/kg did not show any drug-related side effects. The first patient to be treated in this study is still alive and with stable disease 8 months after starting treatment with ImmuPharma’s cancer compound. The second dose level of 2 mg/kg also did not show any drug-related side effects. ImmuPharma has already begun development of the next generation of IPP-204106, the ‘micro Nucants’. This improved formulation comprising of small particles of the drug candidate has shown an even more impressive efficacy in cancer models. The clinical trial is taking place in two hospitals in Paris and one hospital in Dijon, in France and is expected to complete in the coming months. ImmuPharma hopes to start a Phase IIb programme later in 2011 in patients with glioblastoma (brain tumour), hormone-resistant prostate cancer and pancreatic cancer.

 

Prima Biomed Ltd. – Special call to provide updates and commentary around the phase III study of CVac(TM), the unmet medical need of ovarian cancer patients and relevance for the medical oncology profession

 


 

Corporate Finance:

 

Thallion Pharmaceuticals, Inc. announced consolidated earnings results for the fourth quarter and full year ended November 30, 2010. Net loss for the quarter was $1,128,252 or $0.04 per basic and diluted share compared to $4,685,447 or $0.15 per basic and diluted share for the three-month period ended November 30, 2009.

 

Net loss for the year was $4,880,232 or $0.15 per basic and diluted share compared to $13,948,305 or $0.43 per basic and diluted share for the corresponding period in 2009. Revenues were $3,911,772 against $78,247 reported last year. The changes in net loss were mainly attributable to collaboration and licensing revenues beginning in 2010, as well as reductions in R&D expenses, lease exit costs, stock-based compensation expenses and the write-off of capital assets, partially offset by the 2009 gain on the settlement of note receivable with Caprion Proteomics Inc. Net cash flows from operating activities were $932,072 against net cash used in operating activities of $10,715,638 and additions to capital assets were $16,721 against $22,215 reported last year.

 

GTX Inc. reported unaudited consolidated earnings results for the fourth quarter and full year ended December 31, 2010. For the quarter, the company reported total revenue was $1,805,000 against $3,677,000 for the same period a year earlier. Loss from operations was $8,756,000 against $10,937,000 for the same period a year earlier. Loss before income tax was $7,529,000 against $10,919,000 for the same period a year earlier. Net loss was $7,529,000 or $0.16 per basic and diluted share against $10,875,000 or $0.30 per basic and diluted share for the same period a year earlier.

 

For the year, the company reported total revenue was $60,613,000 against $14,730,000 for the same period a year earlier. Income from operations was $13,931,000 against loss from operations of $46,682,000 for the same period a year earlier. Income before income tax was $15,294,000 against loss before income tax of $46,494,000 for the same period a year earlier. Net income was $15,294,000 or $0.39 per basic and diluted share against net loss of $46,256,000 or $1.27 per basic and diluted share for the same period a year earlier.

 

Progen Pharmaceuticals Limited reported consolidated earnings results for the half year ended December 31, 2010. For the period, net loss decreased 61.2% to AUD 3,176,000 or 12.85 cents basic and diluted loss per share compared to a loss of AUD 8,192,000 or 33.16 cents basic and diluted loss per share for the six months ended December 31, 2009. The variance is primarily due to reduced costs of AUD 1.8 million as a result of the settlement with Medigen in 2009, a decrease in research and development expenditure of AUD 1.1 million, a reduction in legal expenses of AUD 826,000 and administrative savings of AUD 516,000. Increased profitability of the company’s manufacturing operations also contributed a AUD 453,000 improvement to the result. Revenue was AUD 1,494,000 against AUD 1,120,000 corresponding period of 2009. Interest income decreased 20.1% from the previous corresponding period to AUD 298,000. This is due to the reduced cash equivalents available for investment due to operating losses sustained during 2010. Net loss from operations was AUD 3,097,000 versus AUD 7,725,000 for the same period last year. Net cash flows used in operating activities were AUD 2,216,000 against AUD 7,640,000 of previous year period. Purchase of property, equipment and other assets was AUD 36,000 versus AUD 21,000 for the same period last year.

 

Caliper Life Sciences, Inc. reported unaudited consolidated earnings results for the fourth quarter and full year ended December 31, 2010. For the quarter, the company reported net loss of $1,434,000 or $0.03 per diluted share and operating loss of $1,000,000 on total revenue of $36,249,000 compared to net income of $5,851,000 or $0.11 per diluted share and operating income of $959,000 on total revenue of $37,656,000 for the same period a year ago. Adjusted earnings was $1,313,000 or $0.02 per diluted share compared to adjusted earnings of $2,479,000 or $0.05 per diluted share for the same period a year ago. The decrease in non-GAAP net income resulted primarily from the impact of a non-recurring significant microfluidic license and settlement agreement in the fourth quarter of 2009. GAAP revenue decreased 4% compared to 2009, due to the impact of divestitures.

 

For the year, the company reported net income of $4,276,000 or $0.08 per diluted share and operating loss of $6,044,000 on total revenue of $123,696,000 compared to net loss of $8,225,000 or $0.17 per diluted share and operating loss of $12,204,000 on total revenue of $130,412,000 for the same period a year ago. Adjusted earnings was $960,000 or $0.02 per diluted share compared to adjusted loss of $5,839,000 or $0.12 per diluted share for the same period a year ago. The increase in non-GAAP net income over 2009 resulted primarily from gross margin improvements achieved in 2010. The company reported positive cash flows from operations of $4.3 million. EBITDA more than tripled to $6.7 million. Non-GAAP EBITDA was $4 million.

 

The company is currently projecting 2011 full year GAAP revenue in the range of $135 million to $145 million including approximately 1% point of anticipated currency benefit. The company expects gross margins 52%-plus. The company is projecting about $4 million to $6 million of EBITDA in 2011. The company expects to report non-GAAP adjusted net loss per share of between $0.03 and $0.05 in 2011. The company is looking at CapEx of roughly $3.5 million.

 

For the first quarter of 2011, the company is projecting GAAP revenues in the range of $32 million to $34.5 million.

 

Exelixis, Inc. reported consolidated unaudited earnings results for the fourth quarter and full year ended December 31, 2010. For the quarter, the company reported total revenues of $40,777,000 against $44,079,000 for the same period a year ago. Loss from operations was $14,109,000 against $30,303,000 a year ago. Consolidated loss before taxes was $17,865,000 against $36,133,000 a year ago. Consolidated net loss was $17,865,000 against $28,833,000 a year ago. Net loss attributable to the company was $17,865,000 or $0.16 per basic and diluted share against $28,833,000 or $0.27 per basic and diluted share a year ago.

 

For the full year, the company reported total revenues of $185,047,000 against $151,759,000 for the same period a year ago. Loss from operations was $91,397,000 against $121,907,000 a year ago. Consolidated loss before taxes was $92,402,000 against $140,843,000 a year ago. Consolidated net loss was $92,330,000 against $139,557,000 a year ago. Net loss attributable to the company was $92,330,000 or $0.85 per basic and diluted share against $135,220,000 or $1.26 per basic and diluted share a year ago. The decrease in net loss attributable to the company from 2009 to 2010 for both the quarter and the full year was primarily due to decreases in operating expenses relating to 2010 restructuring plans and other cost containment measures.

 

For the full year 2011, the company expects revenues in the range of $145 million to $160 million.

 

Telik Inc. reported unaudited earnings results for the fourth quarter and full year ended December 31, 2010. For the quarter, the company has posted net loss of $9.8 million, or $0.18 basic and diluted per share, compared with a net loss of $4.2 million, or $0.08 basic and diluted per share, for the comparable period in 2009. Loss from operations was $10.99 million against $4.26 million a year ago.

 

For the year, net loss was $24.7 million or $0.46 basic and diluted per share, compared with a net loss of $23.7 million, or $0.44 basic and diluted per share, for the year ended December 31, 2009. Loss from operations was $26.05 million against $24.48 million a year ago.

 

For the full year 2011, the company anticipates cash utilization to be in the range of $14.0 million to $15.0 million. Total operating costs and expenses to be in the range of $13.0 million to $15.0 million, which includes stock-based compensation expense of approximately $1.3 million.

 

The shareholders of Novartis AG approved all proposed resolutions at the group’s Annual General Meeting. The shareholders approved a dividend payment of CHF 2.20 per share for 2010 compared to CHF 2.10 in 2009, representing a payout ratio of approximately 55% of net income from continuing operations. Payment for the 2010 dividend will be made with effect from March 1, 2011.

 

The Group confirmed expectations for 2011 to be a year of continued progress in delivering its strategic priorities continuing to drive innovation, growth and productivity across its businesses implementing its strategy to meet the growing needs of patients and aging societies worldwide through its healthcare portfolio. The company further confirmed its guidance for the year and barring unforeseen events, expects to maintain momentum in 2011 and increase group constant currency sales growth around the double-digit mark. With the continuing drive to generate productivity improvements across the Group, Novartis aims to improve constant currency core operating income margin while investing for the future. In addition, in 2011, the company expects the full effect of Alcon acquisition accounting to result in amortization of intangible assets of approximately USD 2.0 billion. Reported sales growth will be lower as a result of the combined effect of price reductions seen in 2010, the full impact of healthcare reform in the US and generic competition.

 

The Shareholders of the company elected Dr. Enrico Vanni to the Board of Directors for a three year term. He is an independent consultant and member of three company boards of directors, including Alcon Inc. The company also announced that Alexandre Jetzer-Chung and Hans-Joerg Rudloff will retire from the Board as they have reached the statutory age limit.

 

ImmunoCellular Therapeutics, Ltd. (OTCBB: IMUC) announced a private placement of 5,200,000 units at a price of $1.55 per unit for gross proceeds of $8,060,000 on February 23, 2011. The transaction will see participation from certain institutional and other investors. Each unit consists of one common share and one warrant to purchase one-half share. Each warrant entitles the holder to purchase one common share at a price of $2.25 per share for a period of five years from closing. Summer Street Research Partners and Dawson James Securities, Inc. will serve as the exclusive placement agents to the company in connection with this transaction.

 

Exelixis, Inc. is looking to raise additional funds. It stated, “We have incurred cumulative net losses of $1,182.1 million through December 31, 2010 and expect to incur losses for the next several years. Our ultimate success depends on the outcome of our research and development activities. We may seek to raise funds through the sale of equity or debt securities or through external borrowings. In addition, we may enter into additional strategic partnerships or collaborative arrangements for the development and commercialization of our compounds. If adequate funds are not available, we will be required to delay, reduce the scope of, or eliminate one or more of our development programs.

 


 

Leadership Review:

 

Spectrum Pharmaceuticals, Inc. announced the appointment of Steven M. Fruchtman, MD, to the position of Vice President of Clinical Development. Dr. Fruchtman will report directly to George Tidmarsh, MD, PhD, the company’s Chief Scientific Officer and Head of Research and Development Operations, and will provide the strategic planning and leadership necessary for managing the Company’s clinical development of belinostat, ZEVALIN(R) and its other pipeline products. Dr. Fruchtman comes to the company from Allos Therapeutics, where he led the development of pralatrexate for Hematologic and Oncologic indications. After a successful academic career at Mount Sinai Hospital and Medical School in New York, where he was Chief of the Stem Cell Transplantation Program, and prior to joining Allos, Dr. Fruchtman was Senior Director of U.S. Clinical Development and Medical Affairs for Novartis Pharmaceuticals. Dr. Fruchtman has served as an external reviewer for the New England Journal of Medicine, Mayo Clinic Proceedings, Experimental Hematology, European Journal of Hematology, Leukemia, and served on the editorial board of The Mount Sinai Journal of Medicine. Dr. Fruchtman is an author of more than 170 lectures, presentations, books, chapters, and abstracts. Dr. Fruchtman received his Bachelor of Arts with Honors from Cornell University, and his MD from New York Medical College.

 


 

Legal & Litigation:

 

Elan Corporation plc and Celgene Corporation announced that Elan Pharma International Ltd. has entered into a settlement and license agreement with Celgene Corporation resolving the patent infringement litigation involving ABRAXANE(R). Elan initiated legal action in 2006 against Abraxis BioScience Inc. Abraxis was acquired by Celgene in October, 2010. In consideration of the terms of the settlement and license agreement, Celgene will pay Elan a one-time fee of $78 million. Elan will not receive any additional payments for sales of ABRAXANE(R), or any other nab(R)-Paclitaxel product in the United States or globally. Celgene will acquire a fully-paid up, exclusive, world-wide license to select Elan U.S. and foreign patents for ABRAXANE(R).

 


 

Mergers & Acquisitions:

 

Several private equity companies intend to place bids for Astra Tech AB, people familiar with matter said. Permira Advisers Ltd, Advent International Corp, Bain Capital LLC and Warburg Pincus LLC are among the private equity companies that are interested in the company. Other potential bidders include Cinven Group Limited and Apax Partners Worldwide LLP. JPMorgan Chase & Co. is handling the sale process. First round bids are due in mid-March, people said. According to media reports, AstraZeneca PLC intend to divest Astra Tech for about $2 billion.

 


 

News & Events:

 

AstraZeneca PLC opened the new global headquarters in Paddington. AstraZeneca will employ around 350 people over three floors in its new headquarter. This includes 90 staff from its global marketing and sales divisions, some of whom are relocating from its US and Brussels operations.

 

Bio-Bridge Science Inc.’s common stock has been deleted from OTC Bulletin Board (OTCBB) effective February 23, 2011, on account of its failure to comply with Rule 15c2-11.

 

Hospira Inc. announced the unveiling of the Hospira MedNet(TM) Portal at the Healthcare Information and Management Systems Society (HIMSS) Annual Conference and Exhibition in Orlando. This web-based application will provide healthcare institutions with advanced medication error reporting and patient safety benchmarking capabilities. It will be available as an add-on feature to the award-winning Hospira MedNet safety software. Hospira MedNet Portal, on demonstration at HIMSS booth 6449, improves a hospital’s ability to monitor, benchmark and evaluate intravenous (I.V.) drug administration practices. With this new technology, healthcare institutions will have access to side-by-side, blinded comparisons of their own safety software drug libraries and infusion performance data with the same information from other institutions. Users can look at data by hospital size, institution type or specific clinical care areas to help them develop and refine their drug library. The software system also allows clinicians and hospital staff to view internal and external peer benchmarking reports to drive improved I.V. medication safety and to help enhance clinical and operational outcomes. Hospira MedNet Portal supports continuous quality improvement efforts by helping users analyze key aspects of their drug administration process against best practices and by providing a more complete picture of clinical performance indicators. Hospira MedNet Portal will be available as a value-added feature for healthcare institutions using Hospira MedNet safety software with their Hospira infusion technologies, such as the Plum A+(TM) with Hospira MedNet safety software, a proven and scaleable infusion pump system; the technologically advanced Symbiq(TM) infusion system with built-in Hospira MedNet; and the market-leading LifeCare PCA(TM) pump with Hospira MedNet. Hospira is also the U.S. leader in I.V. clinical integration of infusion pumps with electronic health record systems. The company is targeting mid-year for making Hospira MedNet Portal available to Hospira MedNet customers.

 


 

Strategy & Strategic Alliances:

 

Yakult Honsha Co. Ltd. signed a development and commercialisation agreement with Proacta, Inc. for anti-cancer drug candidate PR509. Under the agreement, Yakult will conduct preclinical studies and early-Phase clinical trials for PR509 in the United States with Proacta. The terms of the agreement will see the Japanese development and commercialisation rights now belonging to Yakult. No financial detail is disclosed. This co-development agreement in the US and license in Japan are expected to extend Yakult’s current oncology products pipeline such as Campto (irinotecan), Elplat (oxaliplatin) and Opeprim (mitotane) in the long term. PR509 is a pro-drug activated in low oxygen environment, specific for solid tumour cells and targeted for Genentech (US)’s erlotinib and AstraZeneca’s Irressa (geftinib) tolerated in non-small-cell lung cancer, with an eye to widen to stomach cancer, breast cancer and pancreatic cancer in the long run. With Yakult’s support, Proacta will be able to move forward the development of PR509 in the US.

 

Caliper Life Sciences, Inc. and Covaris, Inc. announced a co-marketing agreement which will leverage Covaris’ acoustic DNA shearing platforms and Caliper’s automation and microfluidics technologies to develop automated workflows for next generation sequencing experiments. Caliper has developed a complete suite of solutions for library construction, sample analysis, and nucleic acid fractionation, which significantly reduces manual manipulations, increases throughput and improves sample-to-sample consistency. Covaris sample preparation technology, which is based on its industry-standard Adaptive Focused Acoustic(TM) (AFA) technology, brings quality, speed, and efficiency to biological and chemical sample preparation with the single-sample S220, the multi-sample E220 and high throughput parallel-processing LE220. The isothermal and non-contact Covaris method accelerates next-generation DNA sequencing sample preparation by providing a highly predictable and reproducible DNA shearing instrumentation, consumables, and applications to the next-gen workflow. Caliper’s portfolio of microfluidic and automation solutions that uniquely enable sample preparation for high throughput sequencing. Caliper’s sequencing tools include the LabChip XT for nucleic acid fractionation, the LabChip GX for library quantification and sizing, the recently launched LabChip DS for purity and quality control, the Zephyr(R) Genomics Workstation for automated nucleic acid extraction and reaction setup, and the Sciclone(R) NGS Workstation, which includes validated protocols for library preparation, sequence capture, and sample normalization.

 

MedTrust Online, LLC and Avantra Biosciences Corporation announced a novel collaboration to involve clinicians in the earliest stages of molecular diagnostic assay development for Avantra Biosciences’ revolutionary QPDx(TM) multiplex immunoassay system. The two companies will provide a global community of over 10,000 cancer care professionals with early access to the latest panels of protein biomarkers implicated in different cancers. Avantra, based in Woburn, MA, is a leading innovator in protein diagnostics and recently announced the commercialization of the new Q400 Biomarker Workstation and innovative AngioGenQx(TM) BioChip immunoassay. The system provides quantitative protein biomarker results for ten analytes in less than an hour, requiring only five minutes for sample preparation. As Avantra’s scientific development team identifies biomarkers of interest for its QPDx(TM) system, MedTrust will use its Knowledge Medicine(TM) platform to engage oncologists in online discussions that will validate the role of different panels in diagnosis, prognosis, and treatment efficacy in cancer care. The first of several multiplex assays to be evaluated include an upcoming panel developed in the recently announced collaboration between Avantra and TGen Drug Development. Avantra intends to develop additional panels that may target ovarian, pancreatic, lung, prostate, breast, and colorectal cancers to uncover associations between protein marker levels and patient drug responses that can positively impact clinical decisions. Currently available for research use only (RUO), Avantra intends to seek regulatory approval for its assay technologies as the clinical utility of the molecular information becomes evident. In addition to oncology, Avantra is exploring opportunities in other areas such as infectious disease through its upcoming panel for sepsis.

 

Harris Corp. is teaming with Cancer Treatment Services International L.P. to bring high quality, cost-effective cancer care to patients in regions worldwide. Under the agreement, Harris will serve as the exclusive technology provider for CTSI’s growing network of oncology clinics, including a state-of-the-art facility currently under construction in Hyderabad, India. Harris and CTSI will collaborate to develop and integrate advanced healthcare IT and clinical approaches.

Vital Signs #1 – Oncology – March 14, 2011

By Scott Jordan, Partner — scott@c3f.ca0.myftpupload.com
1. News & Events: Avastin
2. News Summary

News & Events: Avastin 

Precision medicine wherein patient DNA is collected and analyzed to isolate genetic signatures allowing drugs to be tailored to specific patients, is shaping/redefining drug development and given rise to the “omic” sciences: pharmacogenomics, bioinformatics, functional genomics, and oncogenomics.

Pharmacogenomics (PGx), or the science of capturing genetic information to help predict how a patient will respond to a wide variety of drugs, has facilitated “getting the right drug to the right patient at the right time.”  Increasingly, pharma/biotech are utilizing these markers to drill down into specific patient populations and find groups that will respond to more targeted therapies as evidenced by Pfizer’s recent announcement of positive clinical data with crizotinib in non-small cell lung cancer (targeting the ALK gene – diagnostic test needed to identify patients who will respond to the drug).

A result of PGx has been the development of “Biomarkers” which predict the likely efficacy of a particular therapy. In the February 24th issue of the San Francisco Chronicle, “Brilliant Concept for Avastin Fades,” journalist Dermot Dougherty profiles how Avastin drug sales growth rates are at risk of  moderating given disappointing clinical study results (early-stage, advanced cancer, and adjuvant trials) and the absence of effective biomarkers.  While Avastin provides an enormous benefit for select patients (in some cases even a year of disease control), on average the treatment advantage can be small (survival) in relation to the reduction in quality of life.

Government agencies, consumer groups, clinicians and even Roche/Genentech (openness to developing biomarkers for Avastin in metastatic breast cancer) realize early trends toward improved disease free survival (DFS) is not sufficient to treat all patients given limited or no survival benefits and Avastin’s side effect profile (~hypertension; patients given medicine alongside chemotherapy have more side effects than those on traditional cancer drugs alone).  Roche/Genentech is being challenged to develop a predictive biomarker(s) essential to the selection of patients who may benefit from Avastin (similar to Imclone/Lilly’s success in developing an effective EGFR biomarker in colorectal cancer ~Erbitux).
Avastin experienced a meteoric ride following Genentech’s 5 month survival advantage in colorectal cancer when paired with chemotherapy in its landmark 2004 study.  Since then, Avastin has received approval to treat advanced colon, breast, lung, brain, and kidney cancers.  Avastin was the first compound approved based upon the anti-angiogenesis mechanism of action (MoA) theory wherein tumor growth can be halted by turning off a cancer cell’s access to blood.

Roche/Genentech has faced significant “head-winds” as they have traversed into first-line and adjuvant care settings (most profitable segment of oncology).  Recent Phase III trials have failed to show Avastin’s potential in late-stage prostate, advanced stomach, early-stage colon cancers and advanced metastatic breast cancer:

·     Phase III trial in combination with docetaxel and prednisone in mend with hormone-refractory prostate cancer (HRPC0 did not extend overall survival compared to chemotherapy and prednisone alone.

·     Phase III study of Avastin with Xeloda did not extend survival among individuals with inoperable or advanced stomach cancer when compared to chemotherapy alone

·     Phase III (NSABPC-08) of Avastin plus chemotherapy following surgery in patients with early-stage colon did not meet primary endpoint of reducing cancer recurrence (adjuvant setting)

·     In 2010, the U.S. FDA announced it would revoke Avastin’s accelerated approval in metastatic breast cancer after reviewing data from studies that showed the drug did not significantly impact the overall survival for patients

Market pressures/developments in Europe have been equally challenging for Avastin:

·     NICE found the treatment of first-line metastatic breast cancer with Avastin in combination with taxane did not improve patient outcomes compared to alternatives

·   NICE appraisal committee concluded that “for breast cancer patients whose tumors have spread elsewhere in the body treated with Avastin/paclitaxel, may slow the growth and spread of the cancer by 5 months more than paclitaxel alone. However, the committee unable to conclude whether Avastin could extend a patient’s life and no evidence suggested Avastin improved patients’ quality of life more than existing treatments

·     NICE commented that Roche did not submit data to the appraisal committee on biomarkers to stratify best responders to Avastin and biomarker-driven hypotheses (why VEGF agents would work effectively) to support the use of Avastin in taxane-resistant breast cancer

·     NICE calculated an unfavorable cost-effectiveness ratio, given the cost per quality-adjusted life years and is unlikely to pay for Avastin treatment in the metastatic breast cancer population in the UK.

Roche/Genentech’s response to public/private pressures to develop biomarkers has been mixed ranging from inferences that predicting benefits was unlikely due to the heterogenicity amongst tumor types, to recently communicating with the FDA the openness of performing biomarker studies in an effort to regain approval for metastatic breast cancer ($8.7 billion market).

To Roche/Genentech’s credit, the firm raised the possibility of developing biomarkers to clarify the clinical benefit of Avastin in patients with high levels of VEGF-A.  Roche/Genentech had previously tested over 150 (clinical) potential Avastin biomarkers (prognostic/predictive) in a number of tumor types including MBC, pancreatic, gastric, colorectal, lung, brain cancers.
In the E2100 study used to garner accelerated approval for Avastin in metastatic breast cancer in 2008, Roche/Genentech submitted to the FDA biomarker/genomic analyses that confirmed longer survival and protection against drug induced hypertension.  Key markers in the angiogenesis process that were associated with response to therapy were VEGF-A (molecular target of Avastin); PDGFR’s – receptors of VEGF-A; and CD31, endothelial cell-adhesion molecule whose expression may be modulated by VEGF-A.   Patients with higher tumor VEGF-A, CD31, and PDGFRβ expression in the tumor vasculature tended to be more likely to benefit from Avastin treatment plus chemotherapy.  Biomarkers include plasma and tumor markers, circulating endothelial and progenitor cells, imaging, and genetic polymorphisms

·         PGx data linking VEGF-1154 AA and -2578 AA genotypes to an improvement in median overall survival

·         Patients with VEGF-634 CC and -1498 TT genotypes had protection from grade 3-4 hypertension, a common side effect of Avastin

Avastin’s legacy is more than secure as one of the most innovative cancer therapies as further supported by recent positive results in ovarian cancer (Oceans study showed women given a course of chemotherapy plus Avastin, and then Avastin alone, lived longer without their cancer worsening.  However, the lack of effective biomarkers is continuing to impact patients who do not have the “molecular signature” to respond and stands against the tides of personalized medicine.

In the next issue of Lifelines, we will explore how the theory of Avastin killing tumors by cutting of blood supply is being challenged (rather a Vascular Permeability Factor mechanism of action).

Clinical & Regulatory:

Helix BioPharma Corp. announced that it has filed a clinical trial application with the Central Register of Clinical Trials at the Polish Ministry of Health seeking approval to perform its planned Phase I/II clinical safety, tolerability and preliminary efficacy study of its lung cancer drug candidate L-DOS47. L-DOS47 is Helix’s first therapeutic immunoconjugate drug candidate under development based upon the Company’s novel DOS47 technology, which is designed to modify the microenvironmental conditions of cancer cells in a manner that leads to their destruction. L-DOS47 is intended to offer an innovative approach to the first-line treatment of inoperable, locally advanced, recurrent or metastatic, non-small cell lung cancer. The CTA review process in Poland typically requires 60 days, during which the reviewers will decide if an applicant is permitted to proceed with its proposed clinical trial. Additional information may be requested from the applicant, which could extend the review period. About the Planned Phase I/II Study: The proposed Phase I/II study is planned to be an open-label, non-randomized study to evaluate the safety, tolerability and preliminary efficacy of L-DOS47 alone and in combination with chemotherapy or radiation therapy. The study is planned to be conducted in patients with inoperable, locally advanced, recurrent or metastatic non-squamous NSCLC, using a multi-arm design whereby patients will be recruited into one of four treatment arms: (1) L-DOS47 monotherapy; (2) L-DOS47 + vinorelbine; (3) L-DOS47 + vinorelbine + cisplatin; or (4) L-DOS47 + radiation therapy. Vinorelbine, cisplatin and radiation therapy are all common treatments used for NSCLC.

Oncolytics Biotech Inc. announced that enrollment has been completed in a U.K. translational clinical trial investigating intravenous administration of REOLYSIN in patients with metastatic colorectal cancer prior to surgical resection of liver metastases (REO 013). The principal investigator is Professor Alan Melcher of St. James’s University Hospital and the trial is sponsored by the University of Leeds, UK. The trial was an open-label, non-randomized, single centre study of REOLYSIN given intravenously to patients for five consecutive days in advance of their scheduled operations to remove colorectal cancer deposits metastatic to the liver. After surgery, the tumour and surrounding liver tissue were assessed for viral status and anti-tumour effects. The primary objectives of the trial are to assess the presence, replication and anti-cancer effects of reovirus within liver metastases after intravenous administration of REOLYSIN by examination of the resected tumour. Secondary objectives include assessing the anti-tumour activity and safety profile of REOLYSIN, and monitoring the humoral and cellular immune response to REOLYSIN. Eligible patients included those with histologically proven colorectal cancer, planned for potentially curative surgical resection of liver metastases. A total of 10 patients were treated in the study. The results are expected to be fully reported in 2011.

Amgen Inc. announced the publication of results from a pivotal Phase 3 study of 1,776 advanced cancer patients with different types of solid tumors (not including breast and prostate cancer) or multiple myeloma, which compared XGEVA(TM) (denosumab) to Zometa(R) (zoledronic acid) in preventing skeletal-related events (SREs). The study, which appeared in the Journal of Clinical Oncology, found that XGEVA was non-inferior to Zometa in delaying or preventing SREs. XGEVA, the first and only RANK Ligand inhibitor indicated for the prevention of SREs in patients with bone metastases from solid tumors was approved by the U.S. Food and Drug Administration (FDA) on Nov. 18, 2010. The approval was based in part on results described in this publication. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma. For the primary endpoint of this study, the median time to first on-study SRE (defined as fracture, radiation to bone, surgery to bone, or spinal cord compression) was 20.6 months for patients receiving XGEVA and 16.3 months for patients receiving Zometa (hazard ratio 0.84, 95% CI: 0.71-0.98), which is statistically significant for non-inferiority (p=0.0007). Although numerically greater, the delay in the time to first SRE associated with XGEVA was not statistically superior compared to Zometa based upon the statistical testing strategy (adjusted p=0.06) (secondary endpoint). The time to first- and subsequent SRE was also numerically greater but not statistically superior compared to Zometa (hazard ratio 0.90, 95% CI: 0.77-1.04, p=0.14) (secondary endpoint). In a subgroup analysis of patients with multiple myeloma, mortality appeared to be higher for denosumab-treated patients compared to those in the control arm (hazard ratio [95% CI] of 2.26 [1.13, 4.50]; n = 180). The limited number of patients in this subgroup, however, precludes definitive conclusions regarding the effects of XGEVA in multiple myeloma patients.

Fate Therapeutics, Inc. reported preliminary data from an ongoing Phase 1b clinical trial of FT1050 at the 2011 BMT Tandem Meetings in Honolulu, Hawaii. The goal of the Phase 1b trial, which is being conducted at the Dana-Farber Cancer Institute and Massachusetts General Hospital, is to determine the safety and tolerability of introducing FT1050 during the standard course of dual umbilical cord blood transplant in adult patients with hematologic malignancies, such as leukemia and lymphoma, who have undergone nonmyeloablative conditioning therapy. Fate Therapeutics is developing FT1050 to improve the overall efficiency of hematopoietic stem cell (HSC) support by enhancing HSC homing to and proliferation in the bone marrow. In the ongoing Phase 1b clinical trial, after a reduced-intensity conditioning regimen, each patient receives two umbilical cord blood units for hematopoietic reconstitution: one treated ex vivo at the point-of-care with FT1050 and one untreated. Fifteen subjects of an anticipated 21 have been enrolled to date, with the last six having received an umbilical cord blood unit using the current FT1050 treatment protocol designed to enhance activity; the first nine patients received an umbilical cord blood unit using an earlier version of the FT1050 treatment protocol designed to assess safety. The investigators evaluated the safety of FT1050 as well as the time to initial hematopoietic reconstitution, and which cord blood unit ultimately contributed most to blood count recovery. The average time to engraftment for the six patients who were treated under the current protocol was 18.5 days compared to a historic average of approximately 21 days. In addition, five of these six patients engrafted with the FT1050 treated cord blood unit, suggesting that FT1050 may confer preferential engraftment. In all 15 patients, the safety profile did not appear to differ from that of a standard double umbilical cord transplant. To date, only one patient has experienced Grade 2 or higher acute graft versus host disease. Ten of 15 patients remain alive and disease-free. Accrual is ongoing. In addition, Fate Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to FT1050 for the ex vivo treatment of human allogeneic hematopoietic stem cells to enhance stem cell engraftment by treating neutropenia, thrombocytopenia, lymphopenia and anemia. The Company has also received a positive recommendation by the Committee for Orphan Medicinal Products for orphan designation in the European Union.

AB Science S.A. announced publication in The Veterinary Journal of results from a preclinical study showing that masitinib has potential as a chemosensitizer. This study, conducted by Dr Douglas Thamm (VMD, Diplomate ACVIM Oncology; Colorado State University) and colleagues, investigated the ability of masitinib to sensitize different canine cancer cell lines to various chemotherapeutic agents. Results showed that masitinib sensitized numerous tumor cell lines from different origins (breast, bladder, melanoma, lymphoma, etc.) to chemotherapeutic drugs such as doxorubicin, gemcitabine and vinblastine. These data also provide additional weight to findings from studies showing that masitinib can enhance the antiproliferative effects of gemcitabine in human pancreatic cancer, including gemcitabine-resistant cell lines, which is a property not seen with other tyrosine kinase inhibitors (Humbert et al. PLoS One, 2010). Masitinib was the first ever approved anticancer drug in veterinary medicine, receiving approval from the European Medicines Agency (EMA) under the trade name Masivet. Masitinib has also recently become obtainable in the United States under the trade name Kinavet CA-1, having received conditional approval in December 2010 from the US Food and Drug Administration (FDA) for treatment of recurrent or nonresectable Grade II and Grade II cutaneous mast cell tumors in dogs that have not previously received radiotherapy and/or chemotherapy except corticosteroids. AB Science is developing masitinib in veterinary medicine in oncology, including several studies to further investigate masitinib’s potential as a chemosensitizer, as well as in non oncology diseases, such as canine atopic dermatitis or asthma in cats. A summary of masitinib’s veterinary clinical development program is provided below (note that this list of indications reflects the development program of masitinib in veterinary medicine and should not be interpreted as a list of indications for which masitinib has demonstrated efficacy). Besides using the animal health segment as a source of revenues to finance its clinical development program in human medicine, AB Science is also using veterinary medicine as a platform to discover new indications for its lead compound masitinib and translate this use into human medicine.

ImmuPharma PLC announced encouraging results from its ongoing phase I/IIa clinical trial in cancer patients: around half of the cancer patients that have undergone treatment with ImmuPharma’s drug candidate IPP-204106 are in stable condition (their disease has stopped progressing) without any other drug treatment. All the patients that enrolled in the study were suffering from advanced cancer with metastases and had all failed their previous treatments with other existing cancer drugs. The third dose level of IPP-204106 has just begun in the next group of patients. ImmuPharma’s clinical trial began last summer and up to now two lower dose levels have been tested. The initial dose level of 1 mg/kg did not show any drug-related side effects. The first patient to be treated in this study is still alive and with stable disease 8 months after starting treatment with ImmuPharma’s cancer compound. The second dose level of 2 mg/kg also did not show any drug-related side effects. ImmuPharma has already begun development of the next generation of IPP-204106, the ‘micro Nucants’. This improved formulation comprising of small particles of the drug candidate has shown an even more impressive efficacy in cancer models. The clinical trial is taking place in two hospitals in Paris and one hospital in Dijon, in France and is expected to complete in the coming months. ImmuPharma hopes to start a Phase IIb programme later in 2011 in patients with glioblastoma (brain tumour), hormone-resistant prostate cancer and pancreatic cancer.

Prima Biomed Ltd. – Special call to provide updates and commentary around the phase III study of CVac(TM), the unmet medical need of ovarian cancer patients and relevance for the medical oncology profession

Corporate Finance:

Thallion Pharmaceuticals, Inc. announced consolidated earnings results for the fourth quarter and full year ended November 30, 2010. Net loss for the quarter was $1,128,252 or $0.04 per basic and diluted share compared to $4,685,447 or $0.15 per basic and diluted share for the three-month period ended November 30, 2009.

Net loss for the year was $4,880,232 or $0.15 per basic and diluted share compared to $13,948,305 or $0.43 per basic and diluted share for the corresponding period in 2009. Revenues were $3,911,772 against $78,247 reported last year. The changes in net loss were mainly attributable to collaboration and licensing revenues beginning in 2010, as well as reductions in R&D expenses, lease exit costs, stock-based compensation expenses and the write-off of capital assets, partially offset by the 2009 gain on the settlement of note receivable with Caprion Proteomics Inc. Net cash flows from operating activities were $932,072 against net cash used in operating activities of $10,715,638 and additions to capital assets were $16,721 against $22,215 reported last year.

GTX Inc. reported unaudited consolidated earnings results for the fourth quarter and full year ended December 31, 2010. For the quarter, the company reported total revenue was $1,805,000 against $3,677,000 for the same period a year earlier. Loss from operations was $8,756,000 against $10,937,000 for the same period a year earlier. Loss before income tax was $7,529,000 against $10,919,000 for the same period a year earlier. Net loss was $7,529,000 or $0.16 per basic and diluted share against $10,875,000 or $0.30 per basic and diluted share for the same period a year earlier.

For the year, the company reported total revenue was $60,613,000 against $14,730,000 for the same period a year earlier. Income from operations was $13,931,000 against loss from operations of $46,682,000 for the same period a year earlier. Income before income tax was $15,294,000 against loss before income tax of $46,494,000 for the same period a year earlier. Net income was $15,294,000 or $0.39 per basic and diluted share against net loss of $46,256,000 or $1.27 per basic and diluted share for the same period a year earlier.

Progen Pharmaceuticals Limited reported consolidated earnings results for the half year ended December 31, 2010. For the period, net loss decreased 61.2% to AUD 3,176,000 or 12.85 cents basic and diluted loss per share compared to a loss of AUD 8,192,000 or 33.16 cents basic and diluted loss per share for the six months ended December 31, 2009. The variance is primarily due to reduced costs of AUD 1.8 million as a result of the settlement with Medigen in 2009, a decrease in research and development expenditure of AUD 1.1 million, a reduction in legal expenses of AUD 826,000 and administrative savings of AUD 516,000. Increased profitability of the company’s manufacturing operations also contributed a AUD 453,000 improvement to the result. Revenue was AUD 1,494,000 against AUD 1,120,000 corresponding period of 2009. Interest income decreased 20.1% from the previous corresponding period to AUD 298,000. This is due to the reduced cash equivalents available for investment due to operating losses sustained during 2010. Net loss from operations was AUD 3,097,000 versus AUD 7,725,000 for the same period last year. Net cash flows used in operating activities were AUD 2,216,000 against AUD 7,640,000 of previous year period. Purchase of property, equipment and other assets was AUD 36,000 versus AUD 21,000 for the same period last year.

Caliper Life Sciences, Inc. reported unaudited consolidated earnings results for the fourth quarter and full year ended December 31, 2010. For the quarter, the company reported net loss of $1,434,000 or $0.03 per diluted share and operating loss of $1,000,000 on total revenue of $36,249,000 compared to net income of $5,851,000 or $0.11 per diluted share and operating income of $959,000 on total revenue of $37,656,000 for the same period a year ago. Adjusted earnings was $1,313,000 or $0.02 per diluted share compared to adjusted earnings of $2,479,000 or $0.05 per diluted share for the same period a year ago. The decrease in non-GAAP net income resulted primarily from the impact of a non-recurring significant microfluidic license and settlement agreement in the fourth quarter of 2009. GAAP revenue decreased 4% compared to 2009, due to the impact of divestitures.

For the year, the company reported net income of $4,276,000 or $0.08 per diluted share and operating loss of $6,044,000 on total revenue of $123,696,000 compared to net loss of $8,225,000 or $0.17 per diluted share and operating loss of $12,204,000 on total revenue of $130,412,000 for the same period a year ago. Adjusted earnings was $960,000 or $0.02 per diluted share compared to adjusted loss of $5,839,000 or $0.12 per diluted share for the same period a year ago. The increase in non-GAAP net income over 2009 resulted primarily from gross margin improvements achieved in 2010. The company reported positive cash flows from operations of $4.3 million. EBITDA more than tripled to $6.7 million. Non-GAAP EBITDA was $4 million.

The company is currently projecting 2011 full year GAAP revenue in the range of $135 million to $145 million including approximately 1% point of anticipated currency benefit. The company expects gross margins 52%-plus. The company is projecting about $4 million to $6 million of EBITDA in 2011. The company expects to report non-GAAP adjusted net loss per share of between $0.03 and $0.05 in 2011. The company is looking at CapEx of roughly $3.5 million.

For the first quarter of 2011, the company is projecting GAAP revenues in the range of $32 million to $34.5 million.

Exelixis, Inc. reported consolidated unaudited earnings results for the fourth quarter and full year ended December 31, 2010. For the quarter, the company reported total revenues of $40,777,000 against $44,079,000 for the same period a year ago. Loss from operations was $14,109,000 against $30,303,000 a year ago. Consolidated loss before taxes was $17,865,000 against $36,133,000 a year ago. Consolidated net loss was $17,865,000 against $28,833,000 a year ago. Net loss attributable to the company was $17,865,000 or $0.16 per basic and diluted share against $28,833,000 or $0.27 per basic and diluted share a year ago.

For the full year, the company reported total revenues of $185,047,000 against $151,759,000 for the same period a year ago. Loss from operations was $91,397,000 against $121,907,000 a year ago. Consolidated loss before taxes was $92,402,000 against $140,843,000 a year ago. Consolidated net loss was $92,330,000 against $139,557,000 a year ago. Net loss attributable to the company was $92,330,000 or $0.85 per basic and diluted share against $135,220,000 or $1.26 per basic and diluted share a year ago. The decrease in net loss attributable to the company from 2009 to 2010 for both the quarter and the full year was primarily due to decreases in operating expenses relating to 2010 restructuring plans and other cost containment measures.

For the full year 2011, the company expects revenues in the range of $145 million to $160 million.

Telik Inc. reported unaudited earnings results for the fourth quarter and full year ended December 31, 2010. For the quarter, the company has posted net loss of $9.8 million, or $0.18 basic and diluted per share, compared with a net loss of $4.2 million, or $0.08 basic and diluted per share, for the comparable period in 2009. Loss from operations was $10.99 million against $4.26 million a year ago.

For the year, net loss was $24.7 million or $0.46 basic and diluted per share, compared with a net loss of $23.7 million, or $0.44 basic and diluted per share, for the year ended December 31, 2009. Loss from operations was $26.05 million against $24.48 million a year ago.

For the full year 2011, the company anticipates cash utilization to be in the range of $14.0 million to $15.0 million. Total operating costs and expenses to be in the range of $13.0 million to $15.0 million, which includes stock-based compensation expense of approximately $1.3 million.

Novartis AG shareholders approved all proposed resolutions at the group’s Annual General Meeting. The shareholders approved a dividend payment of CHF 2.20 per share for 2010 compared to CHF 2.10 in 2009, representing a payout ratio of approximately 55% of net income from continuing operations. Payment for the 2010 dividend will be made with effect from March 1, 2011.

The Group confirmed expectations for 2011 to be a year of continued progress in delivering its strategic priorities continuing to drive innovation, growth and productivity across its businesses implementing its strategy to meet the growing needs of patients and aging societies worldwide through its healthcare portfolio. The company further confirmed its guidance for the year and barring unforeseen events, expects to maintain momentum in 2011 and increase group constant currency sales growth around the double-digit mark. With the continuing drive to generate productivity improvements across the Group, Novartis aims to improve constant currency core operating income margin while investing for the future. In addition, in 2011, the company expects the full effect of Alcon acquisition accounting to result in amortization of intangible assets of approximately USD 2.0 billion. Reported sales growth will be lower as a result of the combined effect of price reductions seen in 2010, the full impact of healthcare reform in the US and generic competition.

The Shareholders of the company elected Dr. Enrico Vanni to the Board of Directors for a three year term. He is an independent consultant and member of three company boards of directors, including Alcon Inc. The company also announced that Alexandre Jetzer-Chung and Hans-Joerg Rudloff will retire from the Board as they have reached the statutory age limit.

ImmunoCellular Therapeutics, Ltd. (OTCBB: IMUC) announced a private placement of 5,200,000 units at a price of $1.55 per unit for gross proceeds of $8,060,000 on February 23, 2011. The transaction will see participation from certain institutional and other investors. Each unit consists of one common share and one warrant to purchase one-half share. Each warrant entitles the holder to purchase one common share at a price of $2.25 per share for a period of five years from closing. Summer Street Research Partners and Dawson James Securities, Inc. will serve as the exclusive placement agents to the company in connection with this transaction.

Exelixis, Inc. is looking to raise additional funds. It stated, “We have incurred cumulative net losses of $1,182.1 million through December 31, 2010 and expect to incur losses for the next several years. Our ultimate success depends on the outcome of our research and development activities. We may seek to raise funds through the sale of equity or debt securities or through external borrowings. In addition, we may enter into additional strategic partnerships or collaborative arrangements for the development and commercialization of our compounds. If adequate funds are not available, we will be required to delay, reduce the scope of, or eliminate one or more of our development programs.

Leadership Review:

Spectrum Pharmaceuticals, Inc. announced the appointment of Steven M. Fruchtman, MD, to the position of Vice President of Clinical Development. Dr. Fruchtman will report directly to George Tidmarsh, MD, PhD, the company’s Chief Scientific Officer and Head of Research and Development Operations, and will provide the strategic planning and leadership necessary for managing the Company’s clinical development of belinostat, ZEVALIN(R) and its other pipeline products. Dr. Fruchtman comes to the company from Allos Therapeutics, where he led the development of pralatrexate for Hematologic and Oncologic indications. After a successful academic career at Mount Sinai Hospital and Medical School in New York, where he was Chief of the Stem Cell Transplantation Program, and prior to joining Allos, Dr. Fruchtman was Senior Director of U.S. Clinical Development and Medical Affairs for Novartis Pharmaceuticals. Dr. Fruchtman has served as an external reviewer for the New England Journal of Medicine, Mayo Clinic Proceedings, Experimental Hematology, European Journal of Hematology, Leukemia, and served on the editorial board of The Mount Sinai Journal of Medicine. Dr. Fruchtman is an author of more than 170 lectures, presentations, books, chapters, and abstracts. Dr. Fruchtman received his Bachelor of Arts with Honors from Cornell University, and his MD from New York Medical College.

Legal & Litigation:

Elan Corporation PLC and Celgene Corporation announced that Elan Pharma International Ltd. has entered into a settlement and license agreement with Celgene Corporation resolving the patent infringement litigation involving ABRAXANE(R). Elan initiated legal action in 2006 against Abraxis BioScience Inc. Abraxis was acquired by Celgene in October, 2010. In consideration of the terms of the settlement and license agreement, Celgene will pay Elan a one-time fee of $78 million. Elan will not receive any additional payments for sales of ABRAXANE(R), or any other nab(R)-Paclitaxel product in the United States or globally. Celgene will acquire a fully-paid up, exclusive, world-wide license to select Elan U.S. and foreign patents for ABRAXANE(R).

Mergers & Acquisitions:

Several private equity companies intend to place bids for Astra Tech AB, people familiar with matter said. Permira Advisers Ltd, Advent International Corp, Bain Capital LLC and Warburg Pincus LLC are among the private equity companies that are interested in the company. Other potential bidders include Cinven Group Limited and Apax Partners Worldwide LLP. JPMorgan Chase & Co. is handling the sale process. First round bids are due in mid March, people said. According to media reports, AstraZeneca PLC intend to divest Astra Tech for about $2 billion.

News & Events:

AstraZeneca PLC opened the new global headquarters in Paddington. AstraZeneca will employ around 350 people over three floors in its new headquarter. This includes 90 staff from its global marketing and sales divisions, some of whom are relocating from its US and Brussels operations.

Bio-Bridge Science Inc.’s common stock has been deleted from OTC Bulletin Board (OTCBB) effective February 23, 2011, on account of its failure to comply with Rule 15c2-11.

Hospira Inc. announced the unveiling of the Hospira MedNet(TM) Portal at the Healthcare Information and Management Systems Society (HIMSS) Annual Conference and Exhibition in Orlando. This web-based application will provide healthcare institutions with advanced medication error reporting and patient safety benchmarking capabilities. It will be available as an add-on feature to the award-winning Hospira MedNet safety software. Hospira MedNet Portal, on demonstration at HIMSS booth 6449, improves a hospital’s ability to monitor, benchmark and evaluate intravenous (I.V.) drug administration practices. With this new technology, healthcare institutions will have access to side-by-side, blinded comparisons of their own safety software drug libraries and infusion performance data with the same information from other institutions. Users can look at data by hospital size, institution type or specific clinical care areas to help them develop and refine their drug library. The software system also allows clinicians and hospital staff to view internal and external peer benchmarking reports to drive improved I.V. medication safety and to help enhance clinical and operational outcomes. Hospira MedNet Portal supports continuous quality improvement efforts by helping users analyze key aspects of their drug administration process against best practices and by providing a more complete picture of clinical performance indicators. Hospira MedNet Portal will be available as a value-added feature for healthcare institutions using Hospira MedNet safety software with their Hospira infusion technologies, such as the Plum A+(TM) with Hospira MedNet safety software, a proven and scaleable infusion pump system; the technologically advanced Symbiq(TM) infusion system with built-in Hospira MedNet; and the market-leading LifeCare PCA(TM) pump with Hospira MedNet. Hospira is also the U.S. leader in I.V. clinical integration of infusion pumps with electronic health record systems. The company is targeting mid-year for making Hospira MedNet Portal available to Hospira MedNet customers.

Strategy & Strategic Alliances:

Yakult Honsha Co. Ltd. signed a development and commercialisation agreement with Proacta, Inc. for anti-cancer drug candidate PR509. Under the agreement, Yakult will conduct preclinical studies and early-Phase clinical trials for PR509 in the United States with Proacta. The terms of the agreement will see the Japanese development and commercialisation rights now belonging to Yakult. No financial detail is disclosed. This co-development agreement in the US and license in Japan are expected to extend Yakult’s current oncology products pipeline such as Campto (irinotecan), Elplat (oxaliplatin) and Opeprim (mitotane) in the long term. PR509 is a pro-drug activated in low oxygen environment, specific for solid tumour cells and targeted for Genentech (US)’s erlotinib and AstraZeneca’s Irressa (geftinib) tolerated in non-small-cell lung cancer, with an eye to widen to stomach cancer, breast cancer and pancreatic cancer in the long run. With Yakult’s support, Proacta will be able to move forward the development of PR509 in the US.

Caliper Life Sciences, Inc. and Covaris, Inc. announced a co-marketing agreement which will leverage Covaris’ acoustic DNA shearing platforms and Caliper’s automation and microfluidics technologies to develop automated workflows for next generation sequencing experiments. Caliper has developed a complete suite of solutions for library construction, sample analysis, and nucleic acid fractionation, which significantly reduces manual manipulations, increases throughput and improves sample-to-sample consistency. Covaris sample preparation technology, which is based on its industry-standard Adaptive Focused Acoustic(TM) (AFA) technology, brings quality, speed, and efficiency to biological and chemical sample preparation with the single-sample S220, the multi-sample E220 and high throughput parallel-processing LE220. The isothermal and non-contact Covaris method accelerates next-generation DNA sequencing sample preparation by providing a highly predictable and reproducible DNA shearing instrumentation, consumables, and applications to the next-gen workflow. Caliper’s portfolio of microfluidic and automation solutions that uniquely enable sample preparation for high throughput sequencing. Caliper’s sequencing tools include the LabChip XT for nucleic acid fractionation, the LabChip GX for library quantification and sizing, the recently launched LabChip DS for purity and quality control, the Zephyr(R) Genomics Workstation for automated nucleic acid extraction and reaction setup, and the Sciclone(R) NGS Workstation, which includes validated protocols for library preparation, sequence capture, and sample normalization.

MedTrust Online, LLC and Avantra Biosciences Corporation announced a novel collaboration to involve clinicians in the earliest stages of molecular diagnostic assay development for Avantra Biosciences’ revolutionary QPDx(TM) multiplex immunoassay system. The two companies will provide a global community of over 10,000 cancer care professionals with early access to the latest panels of protein biomarkers implicated in different cancers. Avantra, based in Woburn, MA, is a leading innovator in protein diagnostics and recently announced the commercialization of the new Q400 Biomarker Workstation and innovative AngioGenQx(TM) BioChip immunoassay. The system provides quantitative protein biomarker results for ten analytes in less than an hour, requiring only five minutes for sample preparation. As Avantra’s scientific development team identifies biomarkers of interest for its QPDx(TM) system, MedTrust will use its Knowledge Medicine(TM) platform to engage oncologists in online discussions that will validate the role of different panels in diagnosis, prognosis, and treatment efficacy in cancer care. The first of several multiplex assays to be evaluated include an upcoming panel developed in the recently announced collaboration between Avantra and TGen Drug Development. Avantra intends to develop additional panels that may target ovarian, pancreatic, lung, prostate, breast, and colorectal cancers to uncover associations between protein marker levels and patient drug responses that can positively impact clinical decisions. Currently available for research use only (RUO), Avantra intends to seek regulatory approval for its assay technologies as the clinical utility of the molecular information becomes evident. In addition to oncology, Avantra is exploring opportunities in other areas such as infectious disease through its upcoming panel for sepsis.

Harris Corp. is teaming with Cancer Treatment Services International L.P. to bring high quality, cost-effective cancer care to patients in regions worldwide. Under the agreement, Harris will serve as the exclusive technology provider for CTSI’s growing network of oncology clinics, including a state-of-the-art facility currently under construction in Hyderabad, India. Harris and CTSI will collaborate to develop and integrate advanced healthcare IT and clinical approaches.